14-3-3 proteins associate with cdc25 phosphatases.
The cdc25 phosphatases play key roles in cell cycle progression by activating cyclin-dependent kinases. Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases. Genes encoding the human homolog of the 14-3-3 epsilon protein and the previously described 14-3-3 beta protein have been isolated in this screening. 14-3-3 proteins constitute a family of well-conserved eukaryotic proteins that were originally isolated in mammalian brain preparations and that possess diverse biochemical activities related to signal transduction. We present evidence that indicates that cdc25 and 14-3-3 proteins physically interact both in vitro and in vivo. 14-3-3 protein does not, however, affect the phosphatase activity of cdc25A. Raf-1, which is known to bind 14-3-3 proteins, has recently been shown to associate with cdc25A and to stimulate its phosphatase activity. 14-3-3 protein, however, has no effect on the cdc25A-kinase activity of Raf-1. Instead, 14-3-3 may facilitate the association of cdc25 with Raf-1 in vivo, participating in the linkage between mitogenic signaling and the cell cycle machinery.
Conklin
D S
DS
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, NY 11724, USA.
Galaktionov
K
K
Beach
D
D
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification / Q000378:metabolism*; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000302:isolation & purification / Q000378:metabolism; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction; D018411:Spodoptera; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase; D020687:cdc25 Phosphatases
D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D010741:Phospholipases A; D010749:Phosphoprotein Phosphatases; D020687:cdc25 Phosphatases