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

Tetsuzo Tauchi, Gen Sheng Feng, Mark S. Marshall, Randy Shen, Charlie Mantel, Tony Pawson, Hal E. Broxmeyer

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133 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)25206-25211
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number40
StatePublished - Oct 7 1994

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tauchi, T., Feng, G. S., Marshall, M. S., Shen, R., Mantel, C., Pawson, T., & Broxmeyer, H. E. (1994). The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells. Journal of Biological Chemistry, 269(40), 25206-25211.