PKCu is a novel, atypical member of the protein kinase C family

• Published in: The Journal of biological chemistry 1994-02, Vol.269 (8), p.6140-6148
• Main Authors: JOHANNES, F.-J, PRESTLE, J, EIS, S, OBERHAGEMANN, P, PIFZENMAIER, K
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Biological and medical sciences; Cell Line; Chromosome Mapping; Chromosomes, Human, Pair 21; Cloning, Molecular; DNA, Complementary; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Isoenzymes - genetics; Isoenzymes - metabolism; Molecular Sequence Data; Multigene Family; Phorbol Esters - metabolism; Protein Kinase C - genetics; Protein Kinase C - metabolism; Sequence Homology, Amino Acid; Species Specificity; Transferases; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)37580-4

We have isolated the full-length cDNA of a novel human serine/threonine protein kinase gene. The deduced protein sequence shows strong homology to conserved domains of members of the protein kinase C (PKC) subfamily. Homologies reside in the duplex zinc-finger-like cysteine-rich motif and in the protein kinase domain. The lack of the C2 domain of the Ca(2+)-dependent PKCs and the presence of a unique NH2-terminal sequence with a potential signal peptide and a transmembrane domain suggest that PKC mu is a novel member of the subgroup of atypical PKCs. An open reading frame coding for 912 amino acids directs an in vitro translation product with an apparent M(r) of 115,000. In vitro phorbol ester binding studies and kinase assays with lysates of cells overexpressing PKC mu showed phorbol ester-independent kinase activity, autophosphorylation, and, in normal rat kidney (NRK) cells, predominant phosphorylation of a 30-kDa protein at serine residues. Southern analysis revealed that PKC mu is a single copy gene located on human chromosome 21. There is constitutive low level expression of the human PKC mu gene in normal tissues with a single transcript of 3.8 kilobases and elevated expression levels in selected tumor cell lines. These data suggest a role of PKC mu in signal transduction pathways related to growth control.