Src kinase tyrosine phosphorylates PTP1C, a protein tyrosine phosphatase containing Src homology-2 domains that down-regulates cell proliferation.
PTP1C is a non-transmembrane-type protein-tyrosine phosphatase and contains two Src homology-2 (SH2) domains. PTP1C was tyrosine-phosphorylated in SR-3Y1, a v-Src-transformed rat fibroblast cell line. Tyrosine phosphorylation of PTP1C was more prominent when PTP1C was overexpressed in SR-3Y1 cells. PTP1C lacking SH2 domains was also tyrosine-phosphorylated in SR-3Y1 cells, indicating that SH2 domains of PTP1C are not required for tyrosine phosphorylation of PTP1C by v-Src kinase. V-Src kinase catalyzed the phosphorylation of PTP1C in a cell-free system. The growth rate of SR-3Y1 was reduced by the expression of PTP1C in the low-serum medium. Furthermore, overexpression of PTP1C suppressed the anchorage-independent colony formation of SR-3Y1 cells. These results suggest that PTP1C is a direct target for v-Src kinase and may down-regulate the proliferation of cells.
Matozaki
T
T
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Uchida
T
T
Fujioka
Y
Y
Kasuga
M
M
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002461:Cell Line, Transformed; D017931:DNA Primers; D015536:Down-Regulation; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D014443:Tyrosine / Q000378:metabolism
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); 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