Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain
Focal adhesion kinase (125 kDa form; pp125FAK) is a widely expressed non-receptor tyrosine kinase that is implicated in integrin-mediated signal transduction. We have identified a novel means of pp 125FAK regulation in human platelets, in which this kinase undergoes sequential proteolytic modificati...
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| Veröffentlicht in: | Biochemical journal 1996-08, Vol.318 ( Pt 1) (1), p.41-47 |
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| container_title | Biochemical journal |
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| creator | Cooray, P Yuan, Y Schoenwaelder, S M Mitchell, C A Salem, H H Jackson, S P |
| description | Focal adhesion kinase (125 kDa form; pp125FAK) is a widely expressed non-receptor tyrosine kinase that is implicated in integrin-mediated signal transduction. We have identified a novel means of pp 125FAK regulation in human platelets, in which this kinase undergoes sequential proteolytic modification from the native 125 kDa form to 90, 45 and 40 kDa fragments in thrombin-, collagen- and ionophore A23187-stimulated platelets. The proteolysis of pp125FAK was prevented by pretreating platelets with the calpain inhibitors calpeptin or calpain inhibitor-1, and was reproduced in vitro by incubating immunoprecipitated pp125FAK with purified calpain. Proteolysis of pp125FAK resulted in a dramatic reduction in its autokinase activity and led to its dissociation from the cytoskeletal fraction of platelets. These studies define a novel signal-terminating role for calpain, wherein proteolytic modification of pp125FAK attenuates its autokinase activity and induces its subcellular relocation within the cell. |
| doi_str_mv | 10.1042/bj3180041 |
| format | Article |
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We have identified a novel means of pp 125FAK regulation in human platelets, in which this kinase undergoes sequential proteolytic modification from the native 125 kDa form to 90, 45 and 40 kDa fragments in thrombin-, collagen- and ionophore A23187-stimulated platelets. The proteolysis of pp125FAK was prevented by pretreating platelets with the calpain inhibitors calpeptin or calpain inhibitor-1, and was reproduced in vitro by incubating immunoprecipitated pp125FAK with purified calpain. Proteolysis of pp125FAK resulted in a dramatic reduction in its autokinase activity and led to its dissociation from the cytoskeletal fraction of platelets. These studies define a novel signal-terminating role for calpain, wherein proteolytic modification of pp125FAK attenuates its autokinase activity and induces its subcellular relocation within the cell.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/bj3180041</identifier><identifier>PMID: 8761450</identifier><language>eng</language><publisher>England</publisher><subject>Blood Platelets - enzymology ; Calcimycin - pharmacology ; Calpain - antagonists & inhibitors ; Calpain - metabolism ; Cell Adhesion Molecules - metabolism ; Cysteine Proteinase Inhibitors - pharmacology ; Cytoskeleton - enzymology ; Dipeptides - pharmacology ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Glycoproteins - pharmacology ; Humans ; Immunoblotting ; Ionophores - pharmacology ; Molecular Weight ; Peptide Fragments - metabolism ; Phosphorylation ; Phosphotyrosine - metabolism ; Protein-Tyrosine Kinases - metabolism ; Subcellular Fractions - enzymology ; Thrombin - pharmacology</subject><ispartof>Biochemical journal, 1996-08, Vol.318 ( Pt 1) (1), p.41-47</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-3a3e8646ccae24c0765dfef2bbfececfcd286dc5caf7143520b781679114e1c83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1217586/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1217586/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8761450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cooray, P</creatorcontrib><creatorcontrib>Yuan, Y</creatorcontrib><creatorcontrib>Schoenwaelder, S M</creatorcontrib><creatorcontrib>Mitchell, C A</creatorcontrib><creatorcontrib>Salem, H H</creatorcontrib><creatorcontrib>Jackson, S P</creatorcontrib><title>Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>Focal adhesion kinase (125 kDa form; pp125FAK) is a widely expressed non-receptor tyrosine kinase that is implicated in integrin-mediated signal transduction. We have identified a novel means of pp 125FAK regulation in human platelets, in which this kinase undergoes sequential proteolytic modification from the native 125 kDa form to 90, 45 and 40 kDa fragments in thrombin-, collagen- and ionophore A23187-stimulated platelets. The proteolysis of pp125FAK was prevented by pretreating platelets with the calpain inhibitors calpeptin or calpain inhibitor-1, and was reproduced in vitro by incubating immunoprecipitated pp125FAK with purified calpain. Proteolysis of pp125FAK resulted in a dramatic reduction in its autokinase activity and led to its dissociation from the cytoskeletal fraction of platelets. These studies define a novel signal-terminating role for calpain, wherein proteolytic modification of pp125FAK attenuates its autokinase activity and induces its subcellular relocation within the cell.</description><subject>Blood Platelets - enzymology</subject><subject>Calcimycin - pharmacology</subject><subject>Calpain - antagonists & inhibitors</subject><subject>Calpain - metabolism</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Cytoskeleton - enzymology</subject><subject>Dipeptides - pharmacology</subject><subject>Focal Adhesion Kinase 1</subject><subject>Focal Adhesion Protein-Tyrosine Kinases</subject><subject>Glycoproteins - pharmacology</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Ionophores - pharmacology</subject><subject>Molecular Weight</subject><subject>Peptide Fragments - metabolism</subject><subject>Phosphorylation</subject><subject>Phosphotyrosine - metabolism</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Subcellular Fractions - enzymology</subject><subject>Thrombin - pharmacology</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkMFKw0AQhhdRaq0efAAhJ7GH6M5ms7tehFKsigUvel4mm0mbmiYxmxT69qa0FD3NYb75_uFn7Br4PXApHpJVBIZzCSdsCFLz0GhhTtmQCyVDxQWcswvvV5yD5JIP2MBoBTLmQzadVQ6LANMl-bwqg--8RE_BXV2DiGeT93HgCsINLijAMg0aWnQFtjsy2Qb9ZY15ecnOMiw8XR3miH3Nnj-nr-H84-VtOpmHTkaqDSOMyCipnEMS0nGt4jSjTCRJRo5c5lJhVOpih5kGGcWCJ9qA0o8AksCZaMSe9t66S9aUOirbBgtbN_kam62tMLf_N2W-tItqY0GAjo3qBbcHQVP9dORbu869o6LAkqrOW21EnyxED473oGsq7xvKjiHA7a5xe2y8Z2_-fnUkDxVHv-aQe6w</recordid><startdate>19960815</startdate><enddate>19960815</enddate><creator>Cooray, P</creator><creator>Yuan, Y</creator><creator>Schoenwaelder, S M</creator><creator>Mitchell, C A</creator><creator>Salem, H H</creator><creator>Jackson, S P</creator><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960815</creationdate><title>Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain</title><author>Cooray, P ; Yuan, Y ; Schoenwaelder, S M ; Mitchell, C A ; Salem, H H ; Jackson, S P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-3a3e8646ccae24c0765dfef2bbfececfcd286dc5caf7143520b781679114e1c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Blood Platelets - enzymology</topic><topic>Calcimycin - pharmacology</topic><topic>Calpain - antagonists & inhibitors</topic><topic>Calpain - metabolism</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Cytoskeleton - enzymology</topic><topic>Dipeptides - pharmacology</topic><topic>Focal Adhesion Kinase 1</topic><topic>Focal Adhesion Protein-Tyrosine Kinases</topic><topic>Glycoproteins - pharmacology</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Ionophores - pharmacology</topic><topic>Molecular Weight</topic><topic>Peptide Fragments - metabolism</topic><topic>Phosphorylation</topic><topic>Phosphotyrosine - metabolism</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Subcellular Fractions - enzymology</topic><topic>Thrombin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cooray, P</creatorcontrib><creatorcontrib>Yuan, Y</creatorcontrib><creatorcontrib>Schoenwaelder, S M</creatorcontrib><creatorcontrib>Mitchell, C A</creatorcontrib><creatorcontrib>Salem, H H</creatorcontrib><creatorcontrib>Jackson, S P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cooray, P</au><au>Yuan, Y</au><au>Schoenwaelder, S M</au><au>Mitchell, C A</au><au>Salem, H H</au><au>Jackson, S P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>1996-08-15</date><risdate>1996</risdate><volume>318 ( Pt 1)</volume><issue>1</issue><spage>41</spage><epage>47</epage><pages>41-47</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>Focal adhesion kinase (125 kDa form; pp125FAK) is a widely expressed non-receptor tyrosine kinase that is implicated in integrin-mediated signal transduction. We have identified a novel means of pp 125FAK regulation in human platelets, in which this kinase undergoes sequential proteolytic modification from the native 125 kDa form to 90, 45 and 40 kDa fragments in thrombin-, collagen- and ionophore A23187-stimulated platelets. The proteolysis of pp125FAK was prevented by pretreating platelets with the calpain inhibitors calpeptin or calpain inhibitor-1, and was reproduced in vitro by incubating immunoprecipitated pp125FAK with purified calpain. Proteolysis of pp125FAK resulted in a dramatic reduction in its autokinase activity and led to its dissociation from the cytoskeletal fraction of platelets. These studies define a novel signal-terminating role for calpain, wherein proteolytic modification of pp125FAK attenuates its autokinase activity and induces its subcellular relocation within the cell.</abstract><cop>England</cop><pmid>8761450</pmid><doi>10.1042/bj3180041</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biochemical journal, 1996-08, Vol.318 ( Pt 1) (1), p.41-47 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Blood Platelets - enzymology Calcimycin - pharmacology Calpain - antagonists & inhibitors Calpain - metabolism Cell Adhesion Molecules - metabolism Cysteine Proteinase Inhibitors - pharmacology Cytoskeleton - enzymology Dipeptides - pharmacology Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Glycoproteins - pharmacology Humans Immunoblotting Ionophores - pharmacology Molecular Weight Peptide Fragments - metabolism Phosphorylation Phosphotyrosine - metabolism Protein-Tyrosine Kinases - metabolism Subcellular Fractions - enzymology Thrombin - pharmacology |
| title | Focal adhesion kinase (pp125FAK) cleavage and regulation by calpain |
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