Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics
Continuous adhesion formation and disassembly (adhesion turnover) in the protrusions of migrating cells is regulated by unclear mechanisms. We show that p21-activated kinase (PAK)-induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylatio...
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| Veröffentlicht in: | The Journal of cell biology 2006-05, Vol.173 (4), p.587-589 |
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| creator | Nayal, Anjana Webb, Donna J Brown, Claire M Schaefer, Erik M Vicente-Manzanares, Miguel Horwitz, Alan Rick |
| description | Continuous adhesion formation and disassembly (adhesion turnover) in the protrusions of migrating cells is regulated by unclear mechanisms. We show that p21-activated kinase (PAK)-induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin-GIT1 binding and promoting the localization of a GIT1-PIX-PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20-30 s, and resemble those seen with paxillin-S273 phosphorylation. These adhesions appear to be regulated by the GIT1-PIX-PAK module near the leading edge. |
| doi_str_mv | 10.1083/jcb.200509075 |
| format | Article |
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We show that p21-activated kinase (PAK)-induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin-GIT1 binding and promoting the localization of a GIT1-PIX-PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20-30 s, and resemble those seen with paxillin-S273 phosphorylation. 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We show that p21-activated kinase (PAK)-induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin-GIT1 binding and promoting the localization of a GIT1-PIX-PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20-30 s, and resemble those seen with paxillin-S273 phosphorylation. These adhesions appear to be regulated by the GIT1-PIX-PAK module near the leading edge.</description><subject>Actins</subject><subject>Amino Acid Sequence - physiology</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Binding sites</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell Adhesion - physiology</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Movement - physiology</subject><subject>Cell Surface Extensions - metabolism</subject><subject>Cell Surface Extensions - ultrastructure</subject><subject>Cellular biology</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Feedback, Physiological - physiology</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Focal adhesions</subject><subject>Guanine Nucleotide Exchange Factors - metabolism</subject><subject>Hepatocytes</subject><subject>Imaging</subject><subject>Macromolecular Substances - metabolism</subject><subject>Mutation - genetics</subject><subject>Myosin Type II - metabolism</subject><subject>p21-Activated Kinases</subject><subject>Paxillin - genetics</subject><subject>Paxillin - metabolism</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphorylation</subject><subject>Physiological regulation</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>rac GTP-Binding Proteins - metabolism</subject><subject>Rats</subject><subject>Rho Guanine Nucleotide Exchange Factors</subject><subject>Serine - metabolism</subject><subject>Signal transduction</subject><subject>Signal Transduction - physiology</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1r2zAYxsVYWdNux93GZnbozd2rL8u-DErZ2tDCAm1hNyHLcqIgW65kj6Z__ZQmZB8HIaTnp4dH74PQewznGEr6Za3rcwLAoQLBX6EZ5gzyEjN4jWYABOcVJ_wYncS4BgAmGH2DjnEhsMAUZigs1JN1zvbZsPIxrbBxarS-z9SY3ZlABM2c18rZZxMzlV3N73G-mP_MFxc3mfbd4MxTpvomC2Y5pZdbqFmZ-OKQrofgxzC9HJtNrzqr41t01CoXzbv9fooevn-7v7zOb39czS8vbnPNCR1zThhtda3KlJoIZpSqRWkq4LpueEFY0XADmrcN4wQqQktGGg64BMYxaVtGT9HXne8w1Z1ptOnHoJwcgu1U2EivrPxX6e1KLv0vSaCgZSGSwdneIPjHycRRdjZq45zqjZ-iLERVFRiXCfz8H7j2U-jT5yRJc04I2brlO0gHH2Mw7SEJBrmtUqYq5aHKxH_8O_4fet9dAj7sgHUcfTjoDHOcciX5005ulZdqGWyUD3cE0ksMokxDo78BJruscQ</recordid><startdate>20060522</startdate><enddate>20060522</enddate><creator>Nayal, Anjana</creator><creator>Webb, Donna J</creator><creator>Brown, Claire M</creator><creator>Schaefer, Erik M</creator><creator>Vicente-Manzanares, Miguel</creator><creator>Horwitz, Alan Rick</creator><general>The Rockefeller University Press</general><general>Rockefeller University Press</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060522</creationdate><title>Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics</title><author>Nayal, Anjana ; 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We show that p21-activated kinase (PAK)-induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin-GIT1 binding and promoting the localization of a GIT1-PIX-PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20-30 s, and resemble those seen with paxillin-S273 phosphorylation. These adhesions appear to be regulated by the GIT1-PIX-PAK module near the leading edge.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>16717130</pmid><doi>10.1083/jcb.200509075</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins Amino Acid Sequence - physiology Animals Antibodies Binding sites Cell adhesion Cell adhesion & migration Cell Adhesion - physiology Cell Cycle Proteins - metabolism Cell Membrane - metabolism Cell Movement - physiology Cell Surface Extensions - metabolism Cell Surface Extensions - ultrastructure Cellular biology CHO Cells Cricetinae Feedback, Physiological - physiology Fibroblasts Fibrosis Focal adhesions Guanine Nucleotide Exchange Factors - metabolism Hepatocytes Imaging Macromolecular Substances - metabolism Mutation - genetics Myosin Type II - metabolism p21-Activated Kinases Paxillin - genetics Paxillin - metabolism Phosphoproteins - metabolism Phosphorylation Physiological regulation Protein-Serine-Threonine Kinases - metabolism Proteins rac GTP-Binding Proteins - metabolism Rats Rho Guanine Nucleotide Exchange Factors Serine - metabolism Signal transduction Signal Transduction - physiology |
| title | Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics |
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