A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain- containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion

Second Department of Internal Medicine, Kobe University School of Medicine, Chuo-ku, Japan.
Molecular and Cellular Biology (Impact Factor: 4.78). 01/1997; 16(12):6887-99. DOI: 10.1128/MCB.16.12.6887
Source: PubMed


Protein tyrosine phosphatases (PTPases), such as SHP-1 and SHP-2, that contain Src homology 2 (SH2) domains play important
roles in growth factor and cytokine signal transduction pathways. A protein of approximately 115 to 120 kDa that interacts
with SHP-1 and SHP-2 was purified from v-src-transformed rat fibroblasts (SR-3Y1 cells), and the corresponding cDNA was cloned.
The predicted amino acid sequence of the encoded protein, termed SHPS-1 (SHP substrate 1), suggests that it is a glycosylated
receptor-like protein with three immunoglobulin-like domains in its extracellular region and four YXX(L/V/I) motifs, potential
tyrosine phosphorylation and SH2-domain binding sites, in its cytoplasmic region. Various mitogens, including serum, insulin,
and lysophosphatidic acid, or cell adhesion induced tyrosine phosphorylation of SHPS-1 and its subsequent association with
SHP-2 in cultured cells. Thus, SHPS-1 may be a direct substrate for both tyrosine kinases, such as the insulin receptor kinase
or Src, and a specific docking protein for SH2-domain-containing PTPases. In addition, we suggest that SHPS-1 may be a potential
substrate for SHP-2 and may function in both growth factor- and cell adhesion-induced cell signaling.

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