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PMID: 2268301 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Human brain n-chimaerin cDNA encodes a novel phorbol ester receptor.

The Biochemical journal ·Vol. 272 ·No. 3 ·1990-12-15 ·Pages 767-73

Ahmed S, Kozma R, Monfries C, Hall C, Lim HH, Smith P, Lim L

Abstract

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.

MeSH Terms
Amino Acid Sequence Antibodies Brain/metabolism Caenorhabditis elegans Proteins Carrier Proteins Chimerin 1 Cloning, Molecular DNA/genetics Escherichia coli/genetics Humans Kinetics Molecular Sequence Data Molecular Weight Nerve Tissue Proteins/genetics,isolation & purification,metabolism Phorbol 12,13-Dibutyrate/metabolism Phorbol Esters/metabolism Plasmids Protein Kinase C Protein Kinases/genetics Receptors, Drug/genetics,metabolism Recombinant Fusion Proteins/isolation & purification,metabolism Restriction Mapping Sequence Homology, Nucleic Acid
Chemicals
Antibodies Caenorhabditis elegans Proteins Carrier Proteins Chimerin 1 Nerve Tissue Proteins Phorbol Esters Receptors, Drug Recombinant Fusion Proteins phorbol ester binding protein phorbol ester receptor Phorbol 12,13-Dibutyrate DNA Protein Kinases Protein Kinase C
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ahmed S
Institute of Molecular and Cellular Biology, National University of Singapore.
Kozma R
Monfries C
Hall C
Lim H H
Smith P
Lim L
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Published
1990-12-15
Pages
767-73
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1150209
Subset
IM
Grants
Wellcome Trust · United Kingdom
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