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Related Collections Hematopoiesis and Stem Cells Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2000, Vol. 96, No. 10, pp. 3406-3413 HEMATOPOIESIS Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells Thamar B. van Dijk, Emile van den Akker, Martine Parren-van Amelsvoort, Hiroyuki Mano, Bob Löwenberg, and Marieke von Lindern From the Institute of Hematology, Erasmus University Rotterdam, Rotterdam, The Netherlands; Department of Molecular Biology, Jichi Medical School, Kawachi-gun, Tochigi, Japan. Stem cell factor (SCF) has an important role in the proliferation, differentiation, survival, and migration of hematopoietic cells. SCF exerts its effects by binding to cKit, a receptor with intrinsic tyrosine kinase activity. Activation of phosphatidylinositol 3'-kinase (PI3-K) by cKit was previously shown to contribute to many SCF-induced cellular responses. Therefore, PI3-K-dependent signaling pathways activated by SCF were investigated. The PI3-K-dependent activation and phosphorylation of the tyrosine kinase Tec and the adapter molecule p62Dok-1 are reported. The study shows that Tec and Dok-1 form a stable complex with Lyn and 2 unidentified phosphoproteins of 56 and 140 kd. Both the Tec homology and the SH2 domain of Tec were identified as being required for the interaction with Dok-1, whereas 2 domains in Dok-1 appeared to mediate the association with Tec. In addition, Tec and Lyn were shown to phosphorylate Dok-1, whereas phosphorylated Dok-1 was demonstrated to bind to the SH2 domains of several signaling molecules activated by SCF, including Abl, CrkL, SHIP, and PLC-1, but not those of Vav and Shc. These findings suggest that p62Dok-1 may function as an important scaffold molecule in cKit-mediated signaling. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Grech, M. Blazquez-Domingo, A. Kolbus, W. J. Bakker, E. W. Mullner, H. Beug, and M. von Lindern Igbp1 is part of a positive feedback loop in stem cell factor-dependent, selective mRNA translation initiation inhibiting erythroid differentiation Blood, October 1, 2008; 112(7): 2750 - 2760. [Abstract] [Full Text] [PDF] J. Li, J. Quirt, H. Q. Do, K. Lyte, F. Fellows, C. G. Goodyer, and R. Wang Expression of c-Kit receptor tyrosine kinase and effect on beta-cell development in the human fetal pancreas Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E475 - E483. [Abstract] [Full Text] [PDF] C.-H. Ng, S. Xu, and K.-P. 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