PKCU IS A NOVEL, ATYPICAL MEMBER OF THE PROTEIN-KINASE-C FAMILY

We have isolated the full-length cDNA of a novel human serine/threonin e protein kinase gene. The deduced protein sequence shows strong homol ogy to conserved domains of members of the protein kinase C (PRC) subf amily. Homologies reside in the duplex zinc-finger-like cysteine-rich motif and in the protein kinase domain. The lack of the C-2 domain of the Ca2(+)-dependent PKCs and the presence of a unique NH2-terminal se quence with a potential signal peptide and a transmembrane domain sugg est 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 tra nslation product with an apparent M(r) of 115,000. In vitro phorbol es ter binding studies and kinase assays with lysates of cells overexpres sing PKC mu showed phorbol ester-independent kinase activity, autophos phorylation, and, in normal rat kidney (NRK) cells, predominant phosph orylation of a 30-kDa protein at serine residues. Southern analysis re vealed that PKC mu is a single copy gene located on human chromosome 2 1. There is constitutive low level expression of the human PKC mu gene in normal tissues with a single transcript of 3.8 kilobases and eleva ted expression levels in selected tumor cell lines. These data suggest a role of PKC mu in signal transduction pathways related to growth co ntrol.