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 Broxmeyer

Research output: Contribution to journalArticle

133 Citations (Scopus)

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

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Proto-Oncogene Proteins c-kit
Phosphoric Monoester Hydrolases
Stem Cell Factor
Chemical activation
Tyrosine
Protein Tyrosine Phosphatases
src Homology Domains
Non-Receptor Type 11 Protein Tyrosine Phosphatase
Cells
Molecules
Mammals
Proto-Oncogenes
Receptor Protein-Tyrosine Kinases
Glutathione Transferase
Germ Cells
Intercellular Signaling Peptides and Proteins
Fusion reactions
Binding Sites
Tissue
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells. / Tauchi, Tetsuzo; Feng, Gen Sheng; Marshall, Mark S.; Shen, Randy; Mantel, Charlie; Pawson, Tony; Broxmeyer, Hal.

In: Journal of Biological Chemistry, Vol. 269, No. 40, 07.10.1994, p. 25206-25211.

Research output: Contribution to journalArticle

Tauchi, T, Feng, GS, Marshall, MS, Shen, R, Mantel, C, Pawson, T & Broxmeyer, H 1994, 'The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells', Journal of Biological Chemistry, vol. 269, no. 40, pp. 25206-25211.
Tauchi T, Feng GS, Marshall MS, Shen R, Mantel C, Pawson T et al. The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells. Journal of Biological Chemistry. 1994 Oct 7;269(40):25206-25211.
Tauchi, Tetsuzo ; Feng, Gen Sheng ; Marshall, Mark S. ; Shen, Randy ; Mantel, Charlie ; Pawson, Tony ; Broxmeyer, Hal. / The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 40. pp. 25206-25211.
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