FAK Phosphorylation by ERK Primes Ras-Induced Tyrosine Dephosphorylation of FAK Mediated by PIN1 and PTP-PEST
Activated Ras has been found in many types of cancer. However, the mechanism underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling casc...
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| Veröffentlicht in: | Molecular cell 2009-07, Vol.35 (1), p.11-25 |
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| creator | Zheng, Yanhua Xia, Yan Hawke, David Halle, Maxime Tremblay, Michel L. Gao, Xiang Zhou, Xiao Zhen Aldape, Kenneth Cobb, Melanie H. Xie, Keping He, Jie Lu, Zhimin |
| description | Activated Ras has been found in many types of cancer. However, the mechanism underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade. ERK phosphorylates FAK S910 and recruits PIN1 and PTP-PEST, which colocalize with FAK at the lamellipodia of migrating cells. PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. These findings uncover the importance of sequential modification of FAK—by serine phosphorylation, isomerization, and tyrosine dephosphorylation—in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis. |
| doi_str_mv | 10.1016/j.molcel.2009.06.013 |
| format | Article |
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However, the mechanism underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade. ERK phosphorylates FAK S910 and recruits PIN1 and PTP-PEST, which colocalize with FAK at the lamellipodia of migrating cells. PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. These findings uncover the importance of sequential modification of FAK—by serine phosphorylation, isomerization, and tyrosine dephosphorylation—in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2009.06.013</identifier><identifier>PMID: 19595712</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Binding Sites ; Cell Line ; Cell Line, Tumor ; Cell Movement ; Focal Adhesion Protein-Tyrosine Kinases - genetics ; Focal Adhesion Protein-Tyrosine Kinases - metabolism ; Humans ; Immunoblotting ; Mice ; Mice, Nude ; Mitogen-Activated Protein Kinases - genetics ; Mitogen-Activated Protein Kinases - metabolism ; Neoplasm Metastasis ; Neoplasm Transplantation ; Neoplasms, Experimental - genetics ; Neoplasms, Experimental - metabolism ; Neoplasms, Experimental - pathology ; NIH 3T3 Cells ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase - genetics ; Peptidylprolyl Isomerase - metabolism ; Phosphorylation ; Protein Binding ; Protein Tyrosine Phosphatase, Non-Receptor Type 12 - genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 12 - metabolism ; ras Proteins - genetics ; ras Proteins - metabolism ; Serine - metabolism ; SIGNALING ; Transfection ; Tyrosine - metabolism</subject><ispartof>Molecular cell, 2009-07, Vol.35 (1), p.11-25</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-d6ac4919462b6c3bbbd76a62908fded42c5336f87e8c42d8237a51bb4284fb203</citedby><cites>FETCH-LOGICAL-c527t-d6ac4919462b6c3bbbd76a62908fded42c5336f87e8c42d8237a51bb4284fb203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276509004249$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19595712$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zheng, Yanhua</creatorcontrib><creatorcontrib>Xia, Yan</creatorcontrib><creatorcontrib>Hawke, David</creatorcontrib><creatorcontrib>Halle, Maxime</creatorcontrib><creatorcontrib>Tremblay, Michel L.</creatorcontrib><creatorcontrib>Gao, Xiang</creatorcontrib><creatorcontrib>Zhou, Xiao Zhen</creatorcontrib><creatorcontrib>Aldape, Kenneth</creatorcontrib><creatorcontrib>Cobb, Melanie H.</creatorcontrib><creatorcontrib>Xie, Keping</creatorcontrib><creatorcontrib>He, Jie</creatorcontrib><creatorcontrib>Lu, Zhimin</creatorcontrib><title>FAK Phosphorylation by ERK Primes Ras-Induced Tyrosine Dephosphorylation of FAK Mediated by PIN1 and PTP-PEST</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>Activated Ras has been found in many types of cancer. However, the mechanism underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade. ERK phosphorylates FAK S910 and recruits PIN1 and PTP-PEST, which colocalize with FAK at the lamellipodia of migrating cells. PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. These findings uncover the importance of sequential modification of FAK—by serine phosphorylation, isomerization, and tyrosine dephosphorylation—in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Focal Adhesion Protein-Tyrosine Kinases - genetics</subject><subject>Focal Adhesion Protein-Tyrosine Kinases - metabolism</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mitogen-Activated Protein Kinases - genetics</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neoplasms, Experimental - pathology</subject><subject>NIH 3T3 Cells</subject><subject>NIMA-Interacting Peptidylprolyl Isomerase</subject><subject>Peptidylprolyl Isomerase - genetics</subject><subject>Peptidylprolyl Isomerase - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Binding</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 12 - genetics</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 12 - metabolism</subject><subject>ras Proteins - genetics</subject><subject>ras Proteins - metabolism</subject><subject>Serine - metabolism</subject><subject>SIGNALING</subject><subject>Transfection</subject><subject>Tyrosine - metabolism</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtvEzEUhS0EoqXwDxDyit1MbY8f4w1SVVIaUWBUwtrya4ijmXFqTyrl3-MoEQUWrGzZ55577_kAeItRjRHml5t6jIP1Q00QkjXiNcLNM3COkRQVxZw-P92J4OwMvMp5gxCmrJUvwRmWTDKByTkYb64-w24d83Yd037Qc4gTNHu4uC_PKYw-w3udq-XkdtY7uNqnmMPk4Ue__aco9vDg9cW7oOciLSbd8iuGenKwW3VVt_i-eg1e9HrI_s3pvAA_bhar69vq7tun5fXVXWUZEXPluLZUYkk5Mdw2xhgnuOZEorZ33lFiWdPwvhW-tZS4ljRCM2wMJS3tDUHNBfhw9N3uzOid9dOc9KC2ZSGd9irqoP7-mcJa_YyPigjMcCOLwfuTQYoPO59nNYZcwh705OMuKy5oy4Q8COlRaEswOfn-dxOM1IGT2qgjJ3XgpBBXhVMpe_fngE9FJzBPG_gS02PwSWUb_FQYhOTtrFwM_-_wC5eCpkY</recordid><startdate>20090710</startdate><enddate>20090710</enddate><creator>Zheng, Yanhua</creator><creator>Xia, Yan</creator><creator>Hawke, David</creator><creator>Halle, Maxime</creator><creator>Tremblay, Michel L.</creator><creator>Gao, Xiang</creator><creator>Zhou, Xiao Zhen</creator><creator>Aldape, Kenneth</creator><creator>Cobb, Melanie H.</creator><creator>Xie, Keping</creator><creator>He, Jie</creator><creator>Lu, Zhimin</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090710</creationdate><title>FAK Phosphorylation by ERK Primes Ras-Induced Tyrosine Dephosphorylation of FAK Mediated by PIN1 and PTP-PEST</title><author>Zheng, Yanhua ; Xia, Yan ; Hawke, David ; Halle, Maxime ; Tremblay, Michel L. ; Gao, Xiang ; Zhou, Xiao Zhen ; Aldape, Kenneth ; Cobb, Melanie H. ; Xie, Keping ; He, Jie ; Lu, Zhimin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-d6ac4919462b6c3bbbd76a62908fded42c5336f87e8c42d8237a51bb4284fb203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Focal Adhesion Protein-Tyrosine Kinases - genetics</topic><topic>Focal Adhesion Protein-Tyrosine Kinases - metabolism</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mitogen-Activated Protein Kinases - genetics</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Neoplasm Metastasis</topic><topic>Neoplasm Transplantation</topic><topic>Neoplasms, Experimental - genetics</topic><topic>Neoplasms, Experimental - metabolism</topic><topic>Neoplasms, Experimental - pathology</topic><topic>NIH 3T3 Cells</topic><topic>NIMA-Interacting Peptidylprolyl Isomerase</topic><topic>Peptidylprolyl Isomerase - genetics</topic><topic>Peptidylprolyl Isomerase - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 12 - genetics</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 12 - metabolism</topic><topic>ras Proteins - genetics</topic><topic>ras Proteins - metabolism</topic><topic>Serine - metabolism</topic><topic>SIGNALING</topic><topic>Transfection</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zheng, Yanhua</creatorcontrib><creatorcontrib>Xia, Yan</creatorcontrib><creatorcontrib>Hawke, David</creatorcontrib><creatorcontrib>Halle, Maxime</creatorcontrib><creatorcontrib>Tremblay, Michel L.</creatorcontrib><creatorcontrib>Gao, Xiang</creatorcontrib><creatorcontrib>Zhou, Xiao Zhen</creatorcontrib><creatorcontrib>Aldape, Kenneth</creatorcontrib><creatorcontrib>Cobb, Melanie H.</creatorcontrib><creatorcontrib>Xie, Keping</creatorcontrib><creatorcontrib>He, Jie</creatorcontrib><creatorcontrib>Lu, Zhimin</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zheng, Yanhua</au><au>Xia, Yan</au><au>Hawke, David</au><au>Halle, Maxime</au><au>Tremblay, Michel L.</au><au>Gao, Xiang</au><au>Zhou, Xiao Zhen</au><au>Aldape, Kenneth</au><au>Cobb, Melanie H.</au><au>Xie, Keping</au><au>He, Jie</au><au>Lu, Zhimin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FAK Phosphorylation by ERK Primes Ras-Induced Tyrosine Dephosphorylation of FAK Mediated by PIN1 and PTP-PEST</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>2009-07-10</date><risdate>2009</risdate><volume>35</volume><issue>1</issue><spage>11</spage><epage>25</epage><pages>11-25</pages><issn>1097-2765</issn><eissn>1097-4164</eissn><abstract>Activated Ras has been found in many types of cancer. However, the mechanism underlying Ras-promoted tumor metastasis remains unclear. We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade. ERK phosphorylates FAK S910 and recruits PIN1 and PTP-PEST, which colocalize with FAK at the lamellipodia of migrating cells. PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. These findings uncover the importance of sequential modification of FAK—by serine phosphorylation, isomerization, and tyrosine dephosphorylation—in the regulation of FAK activity and, thereby, in Ras-related tumor metastasis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>19595712</pmid><doi>10.1016/j.molcel.2009.06.013</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Binding Sites Cell Line Cell Line, Tumor Cell Movement Focal Adhesion Protein-Tyrosine Kinases - genetics Focal Adhesion Protein-Tyrosine Kinases - metabolism Humans Immunoblotting Mice Mice, Nude Mitogen-Activated Protein Kinases - genetics Mitogen-Activated Protein Kinases - metabolism Neoplasm Metastasis Neoplasm Transplantation Neoplasms, Experimental - genetics Neoplasms, Experimental - metabolism Neoplasms, Experimental - pathology NIH 3T3 Cells NIMA-Interacting Peptidylprolyl Isomerase Peptidylprolyl Isomerase - genetics Peptidylprolyl Isomerase - metabolism Phosphorylation Protein Binding Protein Tyrosine Phosphatase, Non-Receptor Type 12 - genetics Protein Tyrosine Phosphatase, Non-Receptor Type 12 - metabolism ras Proteins - genetics ras Proteins - metabolism Serine - metabolism SIGNALING Transfection Tyrosine - metabolism |
| title | FAK Phosphorylation by ERK Primes Ras-Induced Tyrosine Dephosphorylation of FAK Mediated by PIN1 and PTP-PEST |
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