p34cdc2 is physically associated with and phosphorylated by a cdc2-specific tyrosine kinase.
The mammalian homologue of the yeast cdc2 gene encodes a 34-kilodalton serine/threonine kinase that is a subunit of M phase-promoting factor. Recent studies have shown that p34cdc2 is also a major tyrosine-phosphorylated protein in HeLa cells and that its phosphotyrosine content is cell cycle regulated and related to its kinase activity. Here, we show that cdc2 is physically associated with and phosphorylated in vitro by a highly specific tyrosine kinase. Tyrosine phosphorylation of cdc2 in vitro occurs at tyrosine 15, the same site that is phosphorylated in vivo. The association between the two kinases takes place in the cytosolic compartment and involves cyclin B-associated cdc2. Evidence is presented that a substantial fraction of cytosolic cdc2 is hypophosphorylated, whereas nuclear cdc2 is hyperphosphorylated. Finally, we show that the tyrosine kinase associated with cdc2 may be a 67-kilodalton protein and is distinct from src, abl, fms, and other previously reported tyrosine kinases.
Ferris
D K
DK
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, Frederick, Maryland.
White
G A
GA
Kelvin
D J
DJ
Copeland
T D
TD
Li
C C
CC
Longo
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D016213:Cyclins; D003593:Cytoplasm / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
D016213:Cyclins; D046911:Macromolecular Substances; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase