title: Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells.
abstract: 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 PLCgamma-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.
authors.affiliation: Institute of Hematology, Erasmus University Rotterdam, Rotterdam, The Netherlands. vandijk@hema.fgg.eur.nl
authors.forename: T B
authors.initials: TB
authors.lastname: van Dijk
authors.forename: E
authors.initials: E
authors.lastname: van Den Akker
authors.forename: M P
authors.initials: MP
authors.lastname: Amelsvoort
authors.forename: H
authors.initials: H
authors.lastname: Mano
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.forename: M
authors.initials: M
authors.lastname: von Lindern
mesh_terms: D015153:Blotting, Western; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000494:pharmacology*; D010750:Phosphoproteins / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000494:pharmacology*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured; D018909:src Homology Domains; D019061:src-Family Kinases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D019089:Stem Cell Factor; D019869:Phosphatidylinositol 3-Kinases; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases