Studies on the mechanism of action of protein kinase C and the isolation of molecular clones encoding the enzyme.
Protein kinase C (PKC) plays an important role in signal transduction and the action of phorbol ester tumor promoters, and it is of interest to isolate the coding sequence of this enzyme. Using a 53-base pair synthetic oligonucleotide probe that corresponds to an 18-amino acid peptide obtained from rat brain PKC, we have isolated rat brain cDNA clones corresponding to PKC. We have also isolated several closely related clones. Partial nucleotide sequence analysis of one of the PKC clones (RP41) identifies a 224-amino acid region with approximately 40% homology to the carboxy terminal and catalytic domains of both the cAMP-dependent and cGMP-dependent protein kinases. The levels of mRNA homologous to RP41 are very high in brain; very low but detectable levels are present in heart and liver. A second cDNA (RP16) was only partially sequenced, and based on its predicted amino acid sequence, it shares 65% homology with the corresponding region of the PKC clone RP41. The levels of mRNA corresponding to RP16 are also highest in rat brain, but they are of a different size than those detected with RP41. These and additional results indicate that the gene for the enzyme PKC shares considerable homology with other protein kinases and that PKC itself may belong to a new multigene family. The availability of these cDNA clones should greatly facilitate further studies on the role of PKC in growth control, differentiation, and multistage carcinogenesis.
Weinstein
I B
IB
Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032.
O'Brian
C A
CA
Housey
G M
GM
Johnson
M D
MD
Kirschmeier
P
P
Hsiao
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification*; D005796:Genes; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D051381:Rats; D014158:Transcription, Genetic
D004247:DNA; D011493:Protein Kinase C