Mechanism of c-SRC activation in human melanocytes: elevated level of protein tyrosine phosphatase activity directed against the carboxy-terminal regulatory tyrosine.
Normal human melanocytes, and some human melanoma cell lines, contain c-SRC which is constitutively activated by hypophosphorylation of tyrosine 530. We investigated the possibility that the activation of c-SRC in melanocytes might be attributable to elevated levels of tyrosine 530-directed protein tyrosine phosphatase activity in these cells. We found three times more of this phosphatase activity in cell extracts from melanocytes compared to fibroblasts. The majority of the tyrosine 530-dephosphorylating activity was present in the particulate fraction of cell homogenates, where c-SRC is also located. Treatment of melanocytes with the protein tyrosine phosphatase inhibitor, sodium orthovanadate, caused inactivation of c-SRC. From these results, we conclude that activation of c-SRC in human melanocytes may be attributed to an elevated level of protein tyrosine phosphatase activity directed against tyrosine 530.
O'Connor
T J
TJ
MRC Signal Transduction Group, University of Calgary, Alberta, Canada.
Bjorge
J D
JD
Cheng
H C
HC
Wang
J H
JH
Fujita
D J
DJ
D000595:Amino Acid Sequence; D001681:Biological Assay; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010316:Particle Size; D010455:Peptides / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D012995:Solubility; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D010455:Peptides; D014638:Vanadates; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D017027:Protein Tyrosine Phosphatases