Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatases and their complex formations with Grb2 or Fyn.
Post-translational modification of protein tyrosine phosphatases (PTPs) is implicated in functional modulation of these enzymes. Stomach cancer-associated protein tyrosine phosphatase-1 (SAP-1), as well as protein tyrosine phosphatase receptor type O (PTPRO) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) are receptor-type PTPs (RPTPs), which belong to the R3 subtype RPTP family. Here, we have shown that the carboxyl (COOH)-terminal region of SAP-1 undergoes tyrosine phosphorylation by the treatment with a PTP inhibitor. Src family kinases are important for the tyrosine phosphorylation of SAP-1. Either Grb2 or Fyn, through their Src homology-2 domains, bound to the tyrosine-phosphorylated SAP-1. Moreover, both PTPRO and VE-PTP underwent tyrosine phosphorylation in their COOH-terminal regions. Tyrosine phosphorylation of VE-PTP or PTPRO also promoted their complex formations with Grb2 or Fyn. Forced expression of SAP-1, PTPRO or VE-PTP promoted cell spreading and lamellipodium formation of fibroblasts that expressed an activated form of Ras. In contrast, such effects of non-tyrosine-phosphorylated forms of these RPTPs were markedly smaller than those of wild-type RPTPs. Our results thus suggest that tyrosine phosphorylation of R3 subtype RPTPs promotes their complex formations with Grb2 or Fyn and thus participates in the regulation of cell morphology.
Murata
Yoji
Y
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Mori
Munemasa
M
Kotani
Takenori
T
Supriatna
Yana
Y
Okazawa
Hideki
H
Kusakari
Shinya
S
Saito
Yasuyuki
Y
Ohnishi
Hiroshi
H
Matozaki
Takashi
T
D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D051380:GRB2 Adaptor Protein; D014443:Tyrosine; D051076:Proto-Oncogene Proteins c-fyn; C516890:Ptpro protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3