Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor.
A human brain-specific cDNA encoding n-chimaerin, a protein of predicted molecular mass 34 kDa, has sequence identity with two different proteins: protein kinase C (PKC) at the N-terminus and BCR protein [product of the breakpoint-cluster-region (BCR) gene, involved in Philadelphia chromosome translocation] at the C-terminus [Hall, Monfries, Smith, Lim, Kozma, Ahmed, Vannaisungham, Leung & Lim (1990) J. Mol. Biol. 211, 11-16]. The sequence identity of n-chimaerin with PKC includes the cysteine-rich motif CX2CX13CX2CX7CX7C, and amino acids upstream of the first cysteine residue, but not the kinase domain. This region of PKC has been implicated in the binding of diacylglycerol and phorbol esters in a phospholipid-dependent fashion. Part of this cysteine-rich motif (CX2CX13CX2C) has the potential of forming a 'Zn-finger' structure. Phorbol esters cause a variety of physiological changes and are among the most potent tumour promoters that have been described. PKC is the only known protein target for these compounds. We now report that n-chimaerin cDNA encodes a novel phospholipid-dependent phorbol ester receptor, with the cysteine-rich region being responsible for this activity. This finding has wide implications for previous studies equating phorbol ester binding with the presence of PKC in the brain.
Ahmed
S
S
Institute of Molecular and Cellular Biology, National University of Singapore.
Kozma
R
R
Monfries
C
C
Hall
C
C
Lim
H H
HH
Smith
P
P
Lim
L
L
D000595:Amino Acid Sequence; D000906:Antibodies; D001921:Brain / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D020848:Chimerin 1; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010703:Phorbol Esters / Q000378:metabolism; D010957:Plasmids; D011493:Protein Kinase C; D011494:Protein Kinases / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D000906:Antibodies; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D020848:Chimerin 1; D009419:Nerve Tissue Proteins; D010703:Phorbol Esters; D011955:Receptors, Drug; D011993:Recombinant Fusion Proteins; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D004247:DNA; D011494:Protein Kinases; D011493:Protein Kinase C