Cpk is a novel class of Drosophila PtdIns 3-kinase containing a C2 domain.
We report the identification of a novel class of phosphatidylinositol (PtdIns) 3-kinases whose members contain C-terminal C2 domains. We have isolated Drosophila and murine genes (termed cpk and cpk-m respectively) by polymerase chain reaction amplification of cDNA libraries with degenerate primers corresponding to conserved regions of PtdIns kinases. The amino acid sequences of Cpk and Cpk-m are most similar to that of p110, a family of PtdIns 3-kinases that mediates the responses of cells to mitogenic stimuli. The Cpk and Cpk-m sequences are similar to a large, central region of p110, but differ from p110 at their N and C termini. The N termini of the Cpk proteins do not contain any recognizable protein motif, while the C termini contain "C2 domains," a feature unique among PtdIns kinases. Cpk has an intrinsic PtdIns kinase activity and can phosphorylate PtdIns and PtdIns-4-P, but not PtdIns(4,5)P2, at the D3 position of the inositol ring. Cpk is the first PtdIns 3-kinase identified with this particular substrate specificity. We have identified two potential Cpk-binding proteins, p90 and p190, and have determined that both Cpk and p190 may be tyrosine phosphorylated. This finding suggests that Cpk function may be regulated by tyrosine kinases.
Molz
L
L
Cardiovascular Research Institute and Daiichi Research Center, University of California at San Francisco, 94143, USA.
Chen
Y W
YW
Hirano
M
M
Williams
L T
LT
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D017344:Genes, Insect; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)