Differential phosphorylation of c-Abl in cell cycle determined by cdc2 kinase and phosphatase activity.
The product of the c-abl proto-oncogene (c-Abl) is phosphorylated on three sites during interphase and seven additional sites during mitosis. Two interphase and all mitotic c-Abl sites are phosphorylated by cdc2 kinase isolated from either interphase or mitotic cells, with the mitotic cdc2 having an 11-fold higher activity. Inhibition of phosphatases with okadaic acid in interphase cells leads to the phosphorylation of c-Abl mitotic sites, indicating that those sites are preferentially dephosphorylated during interphase. The differential phosphorylation of c-Abl in the cell cycle is therefore determined by an equilibrium between cdc2 kinase and protein phosphatase activities. Treatment of interphase cells with okadaic acid leads to a rounded morphology similar to that observed during mitosis.
Kipreos
E T
ET
Department of Biology, University of California, San Diego, La Jolla 92093.
Wang
J Y
JY
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase; D002453:Cell Cycle; D002478:Cells, Cultured; D004988:Ethers, Cyclic / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D008970:Molecular Weight; D019319:Okadaic Acid; D010446:Peptide Fragments / Q000302:isolation & purification; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl
D004988:Ethers, Cyclic; D010446:Peptide Fragments; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D019319:Okadaic Acid; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D016203:CDC2 Protein Kinase