Identification and characterization of a myristylated and palmitylated serine/threonine protein kinase.
We report the molecular cloning and initial characterization of a novel fatty 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 palmitylation sites. The protein kinase has been accordingly denoted as the myristylated and palmitylated serine/threonine protein kinase (MPSK). Human and mouse MPSKs share approximately 93% identity at the amino acid level with complete 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 human 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 experiments 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 substrates. Indeed, only PHAS-I was identified as an exogenous substrate which was found to be phosphorylated on threonine and serine residues.
Berson
A E
AE
Department of Cellular Signaling, DNAX Research Institute, Palo Alto, California, 94304, USA.
Young
C
C
Morrison
S L
SL
Fujii
G H
GH
Sheung
J
J
Wu
B
B
Bolen
J B
JB
Burkhardt
A L
AL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008969:Molecular Sequence Data; D019814:Myristic Acid / Q000378:metabolism; D010168:Palmitates / Q000378:metabolism; D020161:Physical Chromosome Mapping; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors
D010168:Palmitates; D014157:Transcription Factors; D019814:Myristic Acid; C486000:Stk16 protein, mouse; D017346:Protein Serine-Threonine Kinases; C418980:STK16 protein, human