Involvement of Fyn kinase in Kit and integrin-mediated Rac activation, cytoskeletal reorganization, and chemotaxis of mast cells
Kit receptor and its ligand stem cell factor (SCF) are critical regulators of mast cell production, proliferation, degranulation, and chemotaxis. In this study, we investigated how Fyn kinase regulates chemotaxis of mast cells toward SCF. On β1-integrin engagement, Fyn-deficient (fyn−/−) mast cells...
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| Veröffentlicht in: | Blood 2007-05, Vol.109 (9), p.3679-3686 |
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| creator | Samayawardhena, Lionel A. Kapur, Reuben Craig, Andrew W.B. |
| description | Kit receptor and its ligand stem cell factor (SCF) are critical regulators of mast cell production, proliferation, degranulation, and chemotaxis. In this study, we investigated how Fyn kinase regulates chemotaxis of mast cells toward SCF. On β1-integrin engagement, Fyn-deficient (fyn−/−) mast cells displayed a striking defect in cell spreading and lamellipodia formation compared to wild-type mast cells. The hematopoietic-specific Src family kinases (Lyn/Fgr/Hck) were not required for initial SCF-induced cell spreading. Reduced SCF-induced activation of Rac1 and Rac2 GTPases, p38 mitogen-activated protein kinase, and filamentous actin polymerization was observed in fyn−/− mast cells compared to wild-type mast cells. Retroviral-mediated expression of Fyn, constitutively active forms of Rac2 or phosphatidylinositol 3-kinase (PI3K) in fyn−/− mast cells rescued defects in SCF-induced cell polarization and chemotaxis of Fyn-deficient mast cells. Thus, we conclude that Fyn kinase plays a unique role upstream of PI3K and Rac GTPases to promote the reorganization of the cytoskeleton during mast cell spreading and chemotaxis. |
| doi_str_mv | 10.1182/blood-2006-11-057315 |
| format | Article |
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In this study, we investigated how Fyn kinase regulates chemotaxis of mast cells toward SCF. On β1-integrin engagement, Fyn-deficient (fyn−/−) mast cells displayed a striking defect in cell spreading and lamellipodia formation compared to wild-type mast cells. The hematopoietic-specific Src family kinases (Lyn/Fgr/Hck) were not required for initial SCF-induced cell spreading. Reduced SCF-induced activation of Rac1 and Rac2 GTPases, p38 mitogen-activated protein kinase, and filamentous actin polymerization was observed in fyn−/− mast cells compared to wild-type mast cells. Retroviral-mediated expression of Fyn, constitutively active forms of Rac2 or phosphatidylinositol 3-kinase (PI3K) in fyn−/− mast cells rescued defects in SCF-induced cell polarization and chemotaxis of Fyn-deficient mast cells. 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In this study, we investigated how Fyn kinase regulates chemotaxis of mast cells toward SCF. On β1-integrin engagement, Fyn-deficient (fyn−/−) mast cells displayed a striking defect in cell spreading and lamellipodia formation compared to wild-type mast cells. The hematopoietic-specific Src family kinases (Lyn/Fgr/Hck) were not required for initial SCF-induced cell spreading. Reduced SCF-induced activation of Rac1 and Rac2 GTPases, p38 mitogen-activated protein kinase, and filamentous actin polymerization was observed in fyn−/− mast cells compared to wild-type mast cells. Retroviral-mediated expression of Fyn, constitutively active forms of Rac2 or phosphatidylinositol 3-kinase (PI3K) in fyn−/− mast cells rescued defects in SCF-induced cell polarization and chemotaxis of Fyn-deficient mast cells. Thus, we conclude that Fyn kinase plays a unique role upstream of PI3K and Rac GTPases to promote the reorganization of the cytoskeleton during mast cell spreading and chemotaxis.</description><subject>Actin Cytoskeleton - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Degranulation - physiology</subject><subject>Cells, Cultured</subject><subject>Chemotaxis - physiology</subject><subject>Enzyme Activation - genetics</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoiesis</subject><subject>Integrins - metabolism</subject><subject>Mast Cells - cytology</subject><subject>Mast Cells - enzymology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-fyn - deficiency</subject><subject>Proto-Oncogene Proteins c-fyn - metabolism</subject><subject>Proto-Oncogene Proteins c-kit - metabolism</subject><subject>rac GTP-Binding Proteins - genetics</subject><subject>rac GTP-Binding Proteins - metabolism</subject><subject>rac1 GTP-Binding Protein - genetics</subject><subject>rac1 GTP-Binding Protein - metabolism</subject><subject>RAC2 GTP-Binding Protein</subject><subject>Signal Transduction - physiology</subject><subject>src-Family Kinases - metabolism</subject><subject>Stem Cell Factor - metabolism</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcFu1DAQtRCILoU_QMgXOBGwnThxLkioolBRCQnB2ZrYk61pYhfbu2I58ek4bNTChZPHem_ezJtHyFPOXnGuxOthCsFWgrG24rxisqu5vEc2XApVMSbYfbJhC9j0HT8hj1L6xhhvaiEfkhPeCV4L1WzIrwu_D9MeZ_SZhpGeHzy9dh4SUufpR5cpeFvKjNvofDWjdZDR0s9gKJjs9pBd8C-pOeSQrnHCDBONGOIWvPu5gouEucI5ZPjh0jJmhpSpwWlKj8mDEaaET9b3lHw9f_fl7EN1-en9xdnby8pI2eWKD7KTEqFvuQTbQsvEIPjIpeqNrUVbG7BjL-thtKrvcbDlHkMrxCiUEE2j6lPy5qh7sxuKC1P8Rpj0TXQzxIMO4PS_iHdXehv2mquukW1TBF6sAjF832HKenZpsQAewy7pjjVMiU4WYnMkmhhSijjeDuFML9HpP9HpJbry18foStuzvxe8a1qzKoTnKwGSgWmM4I1LdzzVcSkL99YplnPuHUadjENvSnQRTdY2uP9v8hugXbqr</recordid><startdate>20070501</startdate><enddate>20070501</enddate><creator>Samayawardhena, Lionel A.</creator><creator>Kapur, Reuben</creator><creator>Craig, Andrew W.B.</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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>20070501</creationdate><title>Involvement of Fyn kinase in Kit and integrin-mediated Rac activation, cytoskeletal reorganization, and chemotaxis of mast cells</title><author>Samayawardhena, Lionel A. ; Kapur, Reuben ; Craig, Andrew W.B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-1b5755ea9615ad6a602b21f1589cd3263cadf953bfd899ebd573b622f28224483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Actin Cytoskeleton - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Degranulation - physiology</topic><topic>Cells, Cultured</topic><topic>Chemotaxis - physiology</topic><topic>Enzyme Activation - genetics</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematopoiesis</topic><topic>Integrins - metabolism</topic><topic>Mast Cells - cytology</topic><topic>Mast Cells - enzymology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-fyn - deficiency</topic><topic>Proto-Oncogene Proteins c-fyn - metabolism</topic><topic>Proto-Oncogene Proteins c-kit - metabolism</topic><topic>rac GTP-Binding Proteins - genetics</topic><topic>rac GTP-Binding Proteins - metabolism</topic><topic>rac1 GTP-Binding Protein - genetics</topic><topic>rac1 GTP-Binding Protein - metabolism</topic><topic>RAC2 GTP-Binding Protein</topic><topic>Signal Transduction - physiology</topic><topic>src-Family Kinases - metabolism</topic><topic>Stem Cell Factor - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Samayawardhena, Lionel A.</creatorcontrib><creatorcontrib>Kapur, Reuben</creatorcontrib><creatorcontrib>Craig, Andrew W.B.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</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>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Samayawardhena, Lionel A.</au><au>Kapur, Reuben</au><au>Craig, Andrew W.B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of Fyn kinase in Kit and integrin-mediated Rac activation, cytoskeletal reorganization, and chemotaxis of mast cells</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2007-05-01</date><risdate>2007</risdate><volume>109</volume><issue>9</issue><spage>3679</spage><epage>3686</epage><pages>3679-3686</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Kit receptor and its ligand stem cell factor (SCF) are critical regulators of mast cell production, proliferation, degranulation, and chemotaxis. In this study, we investigated how Fyn kinase regulates chemotaxis of mast cells toward SCF. On β1-integrin engagement, Fyn-deficient (fyn−/−) mast cells displayed a striking defect in cell spreading and lamellipodia formation compared to wild-type mast cells. The hematopoietic-specific Src family kinases (Lyn/Fgr/Hck) were not required for initial SCF-induced cell spreading. Reduced SCF-induced activation of Rac1 and Rac2 GTPases, p38 mitogen-activated protein kinase, and filamentous actin polymerization was observed in fyn−/− mast cells compared to wild-type mast cells. Retroviral-mediated expression of Fyn, constitutively active forms of Rac2 or phosphatidylinositol 3-kinase (PI3K) in fyn−/− mast cells rescued defects in SCF-induced cell polarization and chemotaxis of Fyn-deficient mast cells. Thus, we conclude that Fyn kinase plays a unique role upstream of PI3K and Rac GTPases to promote the reorganization of the cytoskeleton during mast cell spreading and chemotaxis.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>17213284</pmid><doi>10.1182/blood-2006-11-057315</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actin Cytoskeleton - metabolism Animals Biological and medical sciences Cell Degranulation - physiology Cells, Cultured Chemotaxis - physiology Enzyme Activation - genetics Hematologic and hematopoietic diseases Hematopoiesis Integrins - metabolism Mast Cells - cytology Mast Cells - enzymology Medical sciences Mice Mice, Knockout Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-fyn - deficiency Proto-Oncogene Proteins c-fyn - metabolism Proto-Oncogene Proteins c-kit - metabolism rac GTP-Binding Proteins - genetics rac GTP-Binding Proteins - metabolism rac1 GTP-Binding Protein - genetics rac1 GTP-Binding Protein - metabolism RAC2 GTP-Binding Protein Signal Transduction - physiology src-Family Kinases - metabolism Stem Cell Factor - metabolism |
| title | Involvement of Fyn kinase in Kit and integrin-mediated Rac activation, cytoskeletal reorganization, and chemotaxis of mast cells |
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