Role of p34cdc2-mediated phosphorylations in two-step activation of pp60c-src during mitosis.
Phosphorylation of pp60c-src by p34cdc2 at three amino-proximal serine/threonine residues is temporally correlated with, but insufficient for, mitotic activation of c-Src kinase. The direct cause of activation during mitosis appears to be temporally correlated partial dephosphorylation of Tyr-527, a residue whose phosphorylation strongly suppresses pp60c-src activity. Site-directed mutagenesis of the serine/threonine phosphorylation sites blocks half the mitosis-specific decrease in Tyr-527 phosphorylation and half the increase in pp60c-src kinase activity. We conclude that p34cdc2 partially activates pp60c-src by a two-step process in which its serine/threonine phosphorylations either sensitize pp60c-src to a Tyr-527 phosphatase or desensitize it to a Tyr-527 kinase. Furthermore, additional events, independent of these p34cdc2-mediated phosphorylations, participate in mitotic activation of pp60c-src.
Shenoy
S
S
Department of Pathology, Cornell University, Ithaca, NY 14853.
Chackalaparampil
I
I
Bagrodia
S
S
Lin
P H
PH
Shalloway
D
D
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002645:Chickens; D003062:Codon; D016391:Genes, src; D007700:Kinetics; D051379:Mice; D008938:Mitosis; D008979:Moloney murine leukemia virus / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014357:Trypsin
D003062:Codon; D010748:Phosphopeptides; D016392:Proto-Oncogene Proteins pp60(c-src); D016203:CDC2 Protein Kinase; D014357:Trypsin