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Platelet-derived growth factor-BB (PDGF-BB) regulation of migration and focal adhesion kinase phosphorylation in rabbit aortic vascular smooth muscle cells: roles of phosphatidylinositol 3-kinase and mitogen-activated protein kinases.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Cospedal, Ricardo Abedi, H. Zachary, Ian C. |
| Copyright Year | 1999 |
| Abstract | OBJECTIVE Phosphatidylinositol 3'-kinase (PI3-kinase) is implicated in cell migration and focal adhesion kinase (FAK) phosphorylation. In contrast, it has been proposed that mitogen-activated protein (MAP) kinases are essential for proliferation but may be dissociated from chemotactic signalling. We investigated the roles of PI3-kinase and p42/p44 MAP kinases in cell migration and FAK tyrosine phosphorylation induced by platelet-derived growth factor-BB (PDGF-BB) in rabbit aortic vascular smooth muscle cells (VSMCs). The roles of PI3-kinase and MAP kinase pathways in the chemotactic response to insulin-like growth factor-I (IGF-I) were also examined. METHODS The roles of PI3-kinase and p42/p44 MAP kinases were assessed using the PI3-kinase inhibitors, wortmannin and LY294002, and an inhibitor of MAP kinase kinase, PD98059. PI3-kinase activity was measured by phosphatidylinositol phosphorylation in anti-phosphotyrosine immunoprecipitates and by thin layer chromatography of phosphorylated products. Phosphorylation was assessed by immunoprecipitation with anti-phosphotyrosine antibodies and Western blotting with FAK-specific antibody. Migration was evaluated in a chemotaxis chamber using polycarbonate filters with an 8-mm pore size. RESULTS Neither wortmannin nor LY294002 significantly reduced PDGF-BB stimulation of FAK tyrosine phosphorylation, chemotaxis or immunofluorescent staining of focal adhesions in VSMCs. PD98059, a specific inhibitor of MAP kinase activation, did not inhibit FAK tyrosine phosphorylation but markedly inhibited the migratory response of VSMCs to PDGF-BB. IGF-I also stimulated migration of VSMCs, and, relative to the effect of PDGF-BB, induced smaller increases in PI3-kinase and MAP kinase activities. Both wortmannin and PD98059 partially inhibited the migratory response to IGF-I. CONCLUSIONS PDGF-BB stimulation of both FAK tyrosine phosphorylation and migration in VSMCs are not dependent on activation of PI3-kinase. While PDGF-BB stimulation of FAK tyrosine phosphorylation is not dependent on p42/p44 MAP kinase activation, PDGF-BB and IGF-I both stimulate p42/p44 MAP kinase activity and the chemotactic response to these factors is partially dependent on MAP kinase activation. |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/S0008-6363(98)00232-6 |
| PubMed reference number | 10435043 |
| Journal | Medline |
| Volume Number | 41 |
| Issue Number | 3 |
| Alternate Webpage(s) | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cardiovascres/41/3/10.1016/S0008-6363(98)00232-6/2/41-3-708.pdf?Expires=1493028521&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=JfA9UDZ9Qdg-3V6Ev3MBQJprZKkd1w-Dbovl8KRn2YjZLg0JwcRv2-INOq9g0e9S3lzw5GFzgBV29CtKJ~q3shR7NGY9PLIo2BJGEFTDOeCCk0Rxa0mVySdtbEnnK3hHQDrHOs~uk~M7ek7YXbPALJ4mMVctFbuUL8jVa3p89P1oiu15y1EmCDUXXu2Rf384KYkAlfBImpfKBC7D57~TNqhhRAHPtRKURjk5LUojbzjBq9zt~IjvMSy7rgEDNgxWXQXXuao8CjM~DQVjXCgfyNb21rjJ4R0imObiQsi-TUqWTQonVgdm~vEfUxetZav7VkptDBZYtEz~HGJ7GGWbMQ__ |
| Alternate Webpage(s) | https://watermark.silverchair.com/41-3-708.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlkwggJVBgkqhkiG9w0BBwagggJGMIICQgIBADCCAjsGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMGZCC61B69hUMkUu4AgEQgIICDPlLO_SOKWvb2htDL_QyQlbxPjwjBCKcnrMbzIXrp4Ni6I-kMDKuNxwmSMK35hYzIPxB87sGKcjbpJ6Tx_-p4jVlUUYGN8ilwCb7TzTjlLRbyhkqkMAJXrkDEes8_USEjFR1TgKSrJyfmpebYjgQrSOwV4iydGZzEkeuATlDkK0x_uY5IqaOioWX1vLUi9GuMRpFCwuJR4MSdaCaDSBrGDRBJ0ELEkaXV94HiARN1pP3ArnGdekoYHvUUosqqntYcqGrhJO9lvTfi0RObnFOGQ7Df8rxR81Igtd3jckTmIRD5RHFRmKLXjk97qvl5I4JAu4LgToor1fRVEZFPHXA1Q9e3a89AXGJjQzfjDBbQbgND3Bun807sF7pqJFCw7F_SJLUdzVeyi_PX_7q2Qq3JhU0XJ2fZTKJk4MkWf75vZXWnKZUWkgHuF1SWi_jzz8lgqQv76aRyxINC3xjThzLDiLXjgsuzz7nZK0t7VaNuQDy3AaccJVSatvG9weQnSrD8zON1ZdwH_BsdXBFcqWHIHEUZZeICU-EDIDcCz3zIIwSQAA3-PdozqrWeNUJbJRX5GBr3vTFqNFO42dFmWayhPk9I3WIpDzGD9i1v_0hM8rBOSLUwQXxUTDp-_tNW9m2pFYdYO7qLP281WOABXvG4riNKTxXbuRj2C13bKuPLmkz3qQM2a5h4mGh-KAH |
| Alternate Webpage(s) | http://cardiovascres.oxfordjournals.org/content/41/3/708.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1016/S0008-6363%2898%2900232-6 |
| Journal | Cardiovascular research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
