Cell Growth & Differentiation, Vol 2, Issue 7 343-349, Copyright © 1991 by American Association of Cancer Research
p34cdc2 is physically associated with and phosphorylated by a cdc2-specific tyrosine kinase
DK Ferris, GA White, DJ Kelvin, TD Copeland, CC Li and DL Longo
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, Frederick, Maryland.
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