Two mechanisms activate PTPalpha during mitosis.
We show that, dependent on serine hyperphosphorylation, protein tyrosine phosphatase alpha (PTPalpha) is activated by two different mechanisms during mitosis: its specific activity increases and its inhibitory binding to Grb2 decreases. The latter effect probably abates Grb2 inhibition of the phosphotyrosine displacement process that is required specifically for Src dephosphorylation and causes a mitotic increase in transient PTPalpha-Src binding. Thus, part of the increased protein tyrosine phosphatase activity may be specific for Src family members. These effects cease along with Src activation when cells exit mitosis. Src is not activated in mitosis in PTPalpha-knockout cells, indicating a unique mitotic role for this phosphatase. The activation of PTPalpha, combined with the effects of mitotic Cdc2-mediated phosphorylations of Src, quantitatively accounts for the mitotic activation of Src, indicating that PTPalpha is the membrane-bound, serine phosphorylation-activated, protein tyrosine phosphatase that activates Src during mitosis.
Zheng
X M
XM
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Shalloway
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D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D051380:GRB2 Adaptor Protein; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D007527:Isoenzymes; D011506:Proteins; D012694:Serine; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases