Interactions of protein phosphatase type 1, with a focus on myosin phosphatase
Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where u...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
1999 |
|---|
| Umfang: |
6 |
|---|
| Reproduktion: |
Springer Online Journal Archives 1860-2002 |
|---|---|
| Übergeordnetes Werk: |
in: Molecular and cellular biochemistry - 1973, 190(1999) vom: Jan./Feb., Seite 79-84 |
| Übergeordnetes Werk: |
volume:190 ; year:1999 ; month:01/02 ; pages:79-84 ; extent:6 |
| Links: |
|---|
| Katalog-ID: |
NLEJ198049552 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLEJ198049552 | ||
| 003 | DE-627 | ||
| 005 | 20210705232035.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 070527s1999 xx |||||o 00| ||eng c | ||
| 035 | |a (DE-627)NLEJ198049552 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 245 | 1 | 0 | |a Interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| 264 | 1 | |c 1999 | |
| 300 | |a 6 | ||
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a nicht spezifiziert |b z |2 rdamedia | ||
| 338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
| 520 | |a Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. | ||
| 533 | |f Springer Online Journal Archives 1860-2002 | ||
| 700 | 1 | |a Hartshorne, David J. |4 oth | |
| 700 | 1 | |a Hirano, Katsya |4 oth | |
| 773 | 0 | 8 | |i in |t Molecular and cellular biochemistry |d 1973 |g 190(1999) vom: Jan./Feb., Seite 79-84 |w (DE-627)NLEJ188989099 |w (DE-600)2003615-2 |x 1573-4919 |7 nnns |
| 773 | 1 | 8 | |g volume:190 |g year:1999 |g month:01/02 |g pages:79-84 |g extent:6 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1023/A:1006917032557 |
| 912 | |a GBV_USEFLAG_U | ||
| 912 | |a ZDB-1-SOJ | ||
| 912 | |a GBV_NL_ARTICLE | ||
| 951 | |a AR | ||
| 952 | |d 190 |j 1999 |c 1/2 |h 79-84 |g 6 | ||
| matchkey_str |
article:15734919:1999----::neatosfrtipopaaeyewtaouo |
|---|---|
| hierarchy_sort_str |
1999 |
| publishDate |
1999 |
| allfields |
(DE-627)NLEJ198049552 DE-627 ger DE-627 rakwb eng Interactions of protein phosphatase type 1, with a focus on myosin phosphatase 1999 6 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. Springer Online Journal Archives 1860-2002 Hartshorne, David J. oth Hirano, Katsya oth in Molecular and cellular biochemistry 1973 190(1999) vom: Jan./Feb., Seite 79-84 (DE-627)NLEJ188989099 (DE-600)2003615-2 1573-4919 nnns volume:190 year:1999 month:01/02 pages:79-84 extent:6 http://dx.doi.org/10.1023/A:1006917032557 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 190 1999 1/2 79-84 6 |
| spelling |
(DE-627)NLEJ198049552 DE-627 ger DE-627 rakwb eng Interactions of protein phosphatase type 1, with a focus on myosin phosphatase 1999 6 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. Springer Online Journal Archives 1860-2002 Hartshorne, David J. oth Hirano, Katsya oth in Molecular and cellular biochemistry 1973 190(1999) vom: Jan./Feb., Seite 79-84 (DE-627)NLEJ188989099 (DE-600)2003615-2 1573-4919 nnns volume:190 year:1999 month:01/02 pages:79-84 extent:6 http://dx.doi.org/10.1023/A:1006917032557 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 190 1999 1/2 79-84 6 |
| allfields_unstemmed |
(DE-627)NLEJ198049552 DE-627 ger DE-627 rakwb eng Interactions of protein phosphatase type 1, with a focus on myosin phosphatase 1999 6 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. Springer Online Journal Archives 1860-2002 Hartshorne, David J. oth Hirano, Katsya oth in Molecular and cellular biochemistry 1973 190(1999) vom: Jan./Feb., Seite 79-84 (DE-627)NLEJ188989099 (DE-600)2003615-2 1573-4919 nnns volume:190 year:1999 month:01/02 pages:79-84 extent:6 http://dx.doi.org/10.1023/A:1006917032557 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 190 1999 1/2 79-84 6 |
| allfieldsGer |
(DE-627)NLEJ198049552 DE-627 ger DE-627 rakwb eng Interactions of protein phosphatase type 1, with a focus on myosin phosphatase 1999 6 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. Springer Online Journal Archives 1860-2002 Hartshorne, David J. oth Hirano, Katsya oth in Molecular and cellular biochemistry 1973 190(1999) vom: Jan./Feb., Seite 79-84 (DE-627)NLEJ188989099 (DE-600)2003615-2 1573-4919 nnns volume:190 year:1999 month:01/02 pages:79-84 extent:6 http://dx.doi.org/10.1023/A:1006917032557 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 190 1999 1/2 79-84 6 |
| allfieldsSound |
(DE-627)NLEJ198049552 DE-627 ger DE-627 rakwb eng Interactions of protein phosphatase type 1, with a focus on myosin phosphatase 1999 6 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. Springer Online Journal Archives 1860-2002 Hartshorne, David J. oth Hirano, Katsya oth in Molecular and cellular biochemistry 1973 190(1999) vom: Jan./Feb., Seite 79-84 (DE-627)NLEJ188989099 (DE-600)2003615-2 1573-4919 nnns volume:190 year:1999 month:01/02 pages:79-84 extent:6 http://dx.doi.org/10.1023/A:1006917032557 GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE AR 190 1999 1/2 79-84 6 |
| language |
English |
| source |
in Molecular and cellular biochemistry 190(1999) vom: Jan./Feb., Seite 79-84 volume:190 year:1999 month:01/02 pages:79-84 extent:6 |
| sourceStr |
in Molecular and cellular biochemistry 190(1999) vom: Jan./Feb., Seite 79-84 volume:190 year:1999 month:01/02 pages:79-84 extent:6 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| isfreeaccess_bool |
false |
| container_title |
Molecular and cellular biochemistry |
| authorswithroles_txt_mv |
Hartshorne, David J. @@oth@@ Hirano, Katsya @@oth@@ |
| publishDateDaySort_date |
1999-01-01T00:00:00Z |
| hierarchy_top_id |
NLEJ188989099 |
| id |
NLEJ198049552 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">NLEJ198049552</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20210705232035.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">070527s1999 xx |||||o 00| ||eng c</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)NLEJ198049552</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Interactions of protein phosphatase type 1, with a focus on myosin phosphatase</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1999</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">6</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes.</subfield></datafield><datafield tag="533" ind1=" " ind2=" "><subfield code="f">Springer Online Journal Archives 1860-2002</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hartshorne, David J.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hirano, Katsya</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">in</subfield><subfield code="t">Molecular and cellular biochemistry</subfield><subfield code="d">1973</subfield><subfield code="g">190(1999) vom: Jan./Feb., Seite 79-84</subfield><subfield code="w">(DE-627)NLEJ188989099</subfield><subfield code="w">(DE-600)2003615-2</subfield><subfield code="x">1573-4919</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:190</subfield><subfield code="g">year:1999</subfield><subfield code="g">month:01/02</subfield><subfield code="g">pages:79-84</subfield><subfield code="g">extent:6</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://dx.doi.org/10.1023/A:1006917032557</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ZDB-1-SOJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_NL_ARTICLE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">190</subfield><subfield code="j">1999</subfield><subfield code="c">1/2</subfield><subfield code="h">79-84</subfield><subfield code="g">6</subfield></datafield></record></collection>
|
| series2 |
Springer Online Journal Archives 1860-2002 |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)NLEJ188989099 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| collection |
NL |
| remote_str |
true |
| illustrated |
Not Illustrated |
| issn |
1573-4919 |
| topic_title |
Interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
zu |
| author2_variant |
d j h dj djh k h kh |
| hierarchy_parent_title |
Molecular and cellular biochemistry |
| hierarchy_parent_id |
NLEJ188989099 |
| hierarchy_top_title |
Molecular and cellular biochemistry |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)NLEJ188989099 (DE-600)2003615-2 |
| title |
Interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| spellingShingle |
Interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| ctrlnum |
(DE-627)NLEJ198049552 |
| title_full |
Interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| journal |
Molecular and cellular biochemistry |
| journalStr |
Molecular and cellular biochemistry |
| lang_code |
eng |
| isOA_bool |
false |
| recordtype |
marc |
| publishDateSort |
1999 |
| contenttype_str_mv |
zzz |
| container_start_page |
79 |
| container_volume |
190 |
| physical |
6 |
| format_se |
Elektronische Aufsätze |
| title_sort |
interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| title_auth |
Interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| abstract |
Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. |
| abstractGer |
Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. |
| abstract_unstemmed |
Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes. |
| collection_details |
GBV_USEFLAG_U ZDB-1-SOJ GBV_NL_ARTICLE |
| title_short |
Interactions of protein phosphatase type 1, with a focus on myosin phosphatase |
| url |
http://dx.doi.org/10.1023/A:1006917032557 |
| remote_bool |
true |
| author2 |
Hartshorne, David J. Hirano, Katsya |
| author2Str |
Hartshorne, David J. Hirano, Katsya |
| ppnlink |
NLEJ188989099 |
| mediatype_str_mv |
z |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth |
| up_date |
2024-07-06T10:24:37.817Z |
| _version_ |
1803824899363438592 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">NLEJ198049552</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20210705232035.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">070527s1999 xx |||||o 00| ||eng c</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)NLEJ198049552</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Interactions of protein phosphatase type 1, with a focus on myosin phosphatase</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">1999</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">6</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract It has been established for many years that MLCK is regulated by the intracellular Ca2+ concentration via the formation of the Ca2+-calmodulin-MLCK complex. A more recent discovery has been that the myosin phosphatase may also be regulated. This is manifest at suboptimal Ca2+ levels where under certain conditions (e.g. stimulation with several agonists) the MP is inhibited. The net result being that the extent of myosin phosphorylation for a fixed Ca2+ level is increased, i.e. an enhanced Ca2+-sensitivity. Spurred by this intriguing discovery several laboratories began studies on MP with an emphasis to determine the regulatory, or inhibitory, mechanism. A similar preparation was obtained by 3 laboratories and consisted of a catalytic subunit, PP1δ, plus a large subunit (M130/133 for gizzard, M130 for bladder and M 110 for rat aorta) and a smaller subunit of 20-21 kD. The isolated catalytic subunit has a much lower activity towards phosphorylated myosin than the holoenzyme, thus the non-catalytic subunits may serve as targeting proteins and in addition may play a regulatory role. Because of the difference in activities between the catalytic subunit and holoenzyme, one mechanism of regulation may involve dissociation of the trimeric complex, and such was proposed for the effect of arachidonic acid. Another suggested regulatory mechanism was that phosphorylation of the large subunit in its C-terminal half caused inhibition of phosphatase activity. The two mechanisms need not be mutually exclusive and in addition several kinases could influence the activity of the myosin phosphatase. In order to understand the molecular basis of phosphatase regulation it is necessary to determine the topography of the holoenzyme and identify sites of interaction between subunits and substrate. This work is in progress. Using various truncation mutants of M130/133 it has been determined that the binding sites for both PPlc and substrate are located within the N-terminal part of the molecule. The M20 subunit binds to the C-terminal end, although the functional significance of this is not established. Many questions remain to be answered concerning the biochemistry of the myosin phosphatase. An exciting and challenging focus will be to determine the mechanism(s) of regulation and to unravel the signaling cascade(s) that are initiated by agonist-receptor complex formation. In addition, the location of the MP is not known and it is important to establish which (if any) of the cytoskeletal elements are involved in binding to MP. Finally, it is assumed that the trimeric phosphatase, as discussed above, is specific for myosin dephosphorylation and does not act on other substrates. Because of the breadth of its distribution in different tissues and the wide range of proteins interacting with the ankyrin repeats it is possible that this phosphatase, or variants thereof, has roles in other cellular processes.</subfield></datafield><datafield tag="533" ind1=" " ind2=" "><subfield code="f">Springer Online Journal Archives 1860-2002</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hartshorne, David J.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hirano, Katsya</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">in</subfield><subfield code="t">Molecular and cellular biochemistry</subfield><subfield code="d">1973</subfield><subfield code="g">190(1999) vom: Jan./Feb., Seite 79-84</subfield><subfield code="w">(DE-627)NLEJ188989099</subfield><subfield code="w">(DE-600)2003615-2</subfield><subfield code="x">1573-4919</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:190</subfield><subfield code="g">year:1999</subfield><subfield code="g">month:01/02</subfield><subfield code="g">pages:79-84</subfield><subfield code="g">extent:6</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">http://dx.doi.org/10.1023/A:1006917032557</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">ZDB-1-SOJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_NL_ARTICLE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">190</subfield><subfield code="j">1999</subfield><subfield code="c">1/2</subfield><subfield code="h">79-84</subfield><subfield code="g">6</subfield></datafield></record></collection>
|
| score |
7.40096 |