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• W1428006903 abstract "Research Article1 February 1995free access Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells. H. Serve H. Serve Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author N.S. Yee N.S. Yee Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author G. Stella G. Stella Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author L. Sepp-Lorenzino L. Sepp-Lorenzino Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author J.C. Tan J.C. Tan Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author P. Besmer P. Besmer Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author H. Serve H. Serve Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author N.S. Yee N.S. Yee Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author G. Stella G. Stella Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author L. Sepp-Lorenzino L. Sepp-Lorenzino Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author J.C. Tan J.C. Tan Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author P. Besmer P. Besmer Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. Search for more papers by this author Author Information H. Serve1, N.S. Yee1, G. Stella1, L. Sepp-Lorenzino1, J.C. Tan1 and P. Besmer1 1Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021. The EMBO Journal (1995)14:473-483https://doi.org/10.1002/j.1460-2075.1995.tb07023.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info The pleiotropic effects of the Kit receptor system are mediated by Kit-Ligand (KL) induced receptor autophosphorylation and its association with and activation of distinct second messengers, including phosphatidylinositol 3′-kinase (PI3-kinase), p21ras and mitogen-activated protein kinase (MAPK). To define the role of PI3-kinase, p21ras and MAPK in Kit-mediated cell proliferation, survival and adhesion in bone marrow-derived mast cells (BMMC), mutant Kit receptors were expressed in Wsh/Wsh BMMC lacking endogenous c-kit expression. The introduction of both murine Kit(S) and KitL (isoform containing a four amino acid insert) into Wsh/Wsh BMMC restored KL-induced proliferation, survival and adhesion to fibronectin, as well as activation of PI3-kinase, p21ras and MAPK, and induced expression of c-fos, junB, c-myc and c-myb mRNA. Substitution of tyrosine 719 in the kinase insert with phenylalanine (Y719F) abolished PI3-kinase activation, diminished c-fos and junB induction, and impaired KL-induced adhesion of BMMC to fibronectin. In addition, the Y719F mutation had partial effects on p21ras activation, cell proliferation and survival, while MAP kinase activation was not affected. On the other hand, Y821F substitution impaired proliferation and survival without affecting PI3-kinase, p21ras and MAPK activation, and induction of c-myc, c-myb, c-fos and c-jun mRNA, while KL-induced cell adhesion to fibronectin remained intact. In agreement with a role for PI3-kinase in Kit-mediated cell adhesion, wortmannin blocked Kit-mediated cell adhesion at concentrations known to specifically inhibit PI3-kinase. We conclude, that association of Kit with p85PI3-K, and thus with PI3-kinase activity, is necessary for a full mitogenic as well as adhesive response in mast cells. In contrast, tyrosine 821 is essential for Kit-mediated mitogenesis and survival, but not cell adhesion. Previous ArticleNext Article Volume 14Issue 31 February 1995In this issue RelatedDetailsLoading ..." @default.
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• W1428006903 title "Differential roles of PI3-kinase and Kit tyrosine 821 in Kit receptor-mediated proliferation, survival and cell adhesion in mast cells." @default.
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• W1428006903 doi "https://doi.org/10.1002/j.1460-2075.1995.tb07023.x" @default.
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