PHOSPHORYLATION OF PROTEIN-TYROSINE-PHOSPHATASE PTP-1B ON IDENTICAL SITES SUGGESTS ACTIVATION OF A COMMON SIGNALING PATHWAY DURING MITOSIS AND STRESS-RESPONSE IN MAMMALIAN-CELLS

PTP-1B is a widely expressed non-transmembrane tyrosine-specific phosp hatase. Previous studies indicated that, at mitosis, PTP-1B undergoes phosphorylation on two sites, (352)Ser-Pro-Leu-Asn and (386)Ser-Pro-Al a-Lys. Although the Ser-386 site can be phosphorylated by Cyclin B/Cdc 2 in vitro, the kinase for the Ser-352 site is unknown. known. We have found that these phosphorylation events are not unique to normal mito sis. Instead, treatment with many, but not all, stress stimuli, in par ticular osmotic shock and certain phosphatase and protein synthesis in hibitors, leads to phosphorylation of PTP-1B. Tryptic phosphopeptide a nd mutant analysis reveals that, as in mitosis, stress-induced PTP-1B phosphorylation involves both Ser-352 and Ser-386. Activation of the p roline-directed kinases Erk1/2, JNKs, and p38 was neither necessary no r sufficient for stress-induced PTP-1B phosphorylation. Our data sugge st the existence of a novel mitogen-activated protein kinase pathway i n mammalian cells, which is activated at mitosis and in response to os motic shock and other stresses and results in PTP-1B phosphorylation. This pathway may be similar to the recently described Spc1/Sty1 pathwa y in Schizosaccharomyces pombe.