A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion.
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.
Fujioka
Y
Y
Second Department of Internal Medicine, Kobe University School of Medicine, Chuo-ku, Japan.
Matozaki
T
T
Noguchi
T
T
Iwamatsu
A
A
Yamao
T
T
Takahashi
N
N
Tsuda
M
M
Takada
T
T
Kasuga
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000302:isolation & purification* / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D039842:Neural Cell Adhesion Molecule L1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011971:Receptors, Immunologic; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D016415:Sequence Alignment
D000943:Antigens, Differentiation; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008934:Mitogens; D039842:Neural Cell Adhesion Molecule L1; D011971:Receptors, Immunologic; C501924:Sirpa protein, rat; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases