The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells.

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor, which is important for the normal development of hematopoietic cells, melanoblasts, and germ cells. Autophosphorylation of c-kit receptor on tyrosine creates binding sites for cellular src homology 2 (SH2)-containing signaling molecules. The discovery of phosphotyrosine phosphatases that contain SH2 domains suggests ...
roles for these molecules in growth factor signaling pathways. We found that Syp, a phosphotyrosine phosphatase widely expressed in all the tissues in mammals, associates with c-kit receptor after activation with its ligand, steel factor, in the factor-dependent cell line, M07e. Both NH2-terminal and COOH-terminal SH2 domains of Syp, made as glutathione S-transferase fusion proteins, were able to bind to the activated c-kit receptor in vitro. Furthermore, Syp became marginally phosphorylated on tyrosine upon c-kit receptor activation, and tyrosine-phosphorylated Syp was found to be complexed with Grb2 in steel factor-stimulated M07e cells. Direct binding between Syp and Grb2 was also observed in vitro. Last, Ras and Raf interacts in vitro as a result of steel factor-stimulated Ras activation. These results suggest that Syp may be an important signaling component downstream of the c-kit receptor and involved in activation of the Ras signaling pathway in hematopoietic cells.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Line, GRB2 Adaptor Protein, Hematopoietic Cell Growth Factors, Humans, Intracellular Signaling Peptides and Proteins, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-kit, Proto-Oncogene Proteins c-raf, Proto-Oncogene Proteins p21(ras), Receptor Protein-Tyrosine Kinases, Receptors, Colony-Stimulating Factor, Signal Transduction, Stem Cell Factor
J. Biol. Chem.
Date: Oct. 07, 1994
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