Tyrosine dephosphorylation of pp60c-src is stimulated by a serine/threonine phosphatase inhibitor
Chackalaparampil, I.; Bagrodia, S.; Shalloway, D.
Oncogene 9(7): 1947-1955
1994
ISSN/ISBN: 0950-9232 PMID: 7516061 Document Number: 436357
Incubation of NIH3T3-derived c-src overexpressor cells with okadaic acid, a specific serine/threonine phosphatase inhibitor, stimulates pp60-c-src kinase activity about 2-3-fold. Activation is blocked if cells are simultaneously treated with orthovanadate, a tyrosine phosphatase inhibitor. Furthermore, okadaic acid treatment induces a small decrease in Tyr 527 phosphorylation of wild-type pp60-c-src and a large decrease in Tyr 527 phosphorylation of kinase-defective pp60-c-src (Lys fwdarw 29 fwdarw Arg). These results suggest that the activation is mediated by okadaic acid-induced changes in tyrosine phosphorylation of pp60-c-src involving 'cross-over' from serine/threonine to tyrosine signal transduction pathways. Stimulation of pp60-c-src activity and Tyr 527 dephosphorylation do not require changes in serine/threonine phosphorylation of pp60-c-src, suggesting that these changes result from modulation of an upstream Tyr 527 phosphatase or kinase which is itself regulated by altered serine/ threonine phosphorylation. Since okadaic acid induces a pseudomitotic phenotype in rodent cells (K. Yamashita, H. Yasuda, J. Pines, K. Yasumoto, H. Nishitani, M. Ohtsubo, T. Hunter, T. Sugimura and T. Nishimoto, EMBO J., 9: 4331 -4338, 1990), it is possible that these phenomena are induced by a biochemical mechanism similar to that which causes transient tyrosine dephosphorylation of pp60-c-src during mitosis.