Kit signaling through PI 3-kinase and Src kinase pathways: An essential role for Rac1 and JNK activation in mast cell proliferation Journal Article
| Authors: | Timokhina, I.; Kissel, H.; Stella, G.; Besmer, P. |
| Article Title: | Kit signaling through PI 3-kinase and Src kinase pathways: An essential role for Rac1 and JNK activation in mast cell proliferation |
| Abstract: | The receptor tyrosine kinase Kit plays critical roles in hematopoiesis, gametogenesis and melanogenesis. In mast cells, Kit receptor activation mediates several cellular responses including cell proliferation and suppression of apoptosis induced by growth factor deprivation and γ-irradiation. Kit receptor functions are mediated by kinase activation, receptor autophosphorylation and association with various signaling molecules. We have investigated the role of phosphatidylinositol 3'-kinase (PI 3-kinase) and Src kinases in Kit-mediated cell proliferation and suppression of apoptosis induced both by factor deprivation and irradiation in bone marrow-derived mast cells (BMMC). Analysis of Kit(-/-) BMMC expressing mutant Kit receptors and the use of pharmacological inhibitors revealed that both signaling pathways contribute to these Kit-mediated responses and that elimination of both pathways abolishes them. We demonstrate that the PI 3-kinase and Src kinase signaling pathways converge to activate Rac1 and JNK. Analysis of BMMC expressing wild-type and dominant-negative mutant forms of Rac1 and JNK revealed that the Rac1/ JNK pathway is critical for Kit ligand (KL)-induced proliferation of mast cells but not for suppression of apoptosis. In addition, KL was shown to inhibit sustained activation of JNK induced by γ-irradiation and concomitant irradiation-induced apoptosis. |
| Keywords: | signal transduction; controlled study; mutation; nonhuman; cell proliferation; animal cell; mouse; animals; mice; cell division; stem cell factor; proto-oncogene proteins c-kit; apoptosis; gtp-binding proteins; enzyme activation; transfection; protein tyrosine kinase; phosphorylation; phosphatidylinositol 3 kinase; animalia; mice, inbred strains; 1-phosphatidylinositol 3-kinase; gamma irradiation; kit; mitogen-activated protein kinases; src-family kinases; guanine nucleotide binding protein; protein kinase; jnk mitogen-activated protein kinases; mast cell; mast cells; rac gtp-binding proteins; src kinase; rac1; jnk; ca(2+)-calmodulin dependent protein kinase; priority journal; article; phosphatidylinositol 3'-kinase |
| Journal Title: | EMBO Journal |
| Volume: | 17 |
| Issue: | 21 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1998-11-02 |
| Start Page: | 6250 |
| End Page: | 6262 |
| Language: | English |
| DOI: | 10.1093/emboj/17.21.6250 |
| PUBMED: | 9799234 |
| PROVIDER: | scopus |
| PMCID: | PMC1170951 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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