Identification and characterization of a myristylated and palmitylated serine threonine protein kinase

We report the molecular cloning and initial characterization of a novel fat ty acid acylated serine/threonine protein kinase. The putative open reading frame is predicted to encode a 305 amino acid protein possessing a carboxy -terminal protein kinase domain and amino-terminal myristylation and palmit ylation sites. The protein kinase has been accordingly denoted as the myris tylated and palmitylated serine/threonine protein kinase (MPSK). Human and mouse MPSKs share approximately 93% identity at the amino acid level with c omplete retention of acylation sites. Radiation hybridization localized the human MPSK gene to chromosome 2q34-37. Northern analysis demonstrated that the human MPSK 1.7 kilobase mRNA is widely distributed. Epitope tagged hum an MPSK was found to be acylated by myristic acid at glycine residue 2 and by palmitic acid at cysteines 6 and/or 8. Palmitylation of MPSK in these ex periments was found to require an intact myristylation site. While epitope tagged MPSK in immune complexes or purified human glutathione S transferase -MPSK was found to autophosphorylate at one or more threonine residues, the enzyme was not found to phosphorylate several other common exogenous subst rates. Indeed, only PHAS-I was identified as an exogenous substrate which w as found to be phosphorylated on threonine and serine residues, (C) 1999 Ac ademic Press.