Molecular cloning and tissue distribution of PHAS-I, an intracellular target for insulin and growth factors.
Although the actions of insulin and a number of growth factors that signal via protein-tyrosine kinase receptors are believed to involve increased phosphorylation of key intracellular proteins, relatively few of the downstream phosphoproteins have been identified. In this report we describe a cDNA encoding one of the most prominent insulin-stimulated phosphoproteins in rat adipocytes. The cDNA encodes a protein, designated PHAS-I, which has 117 amino acids and a M(r) of 12,400. When translated in vitro and subjected to SDS/PAGE, PHAS-I migrates anomalously, having an apparent M(r) of 21,000. The predicted amino acid composition is interesting in that approximately 45% of the PHAS-I protein is accounted for by only four amino acids--serine, threonine, proline, and glycine. The PHAS-I gene is expressed in a variety of tissues, although the highest levels of mRNA are present in fat and skeletal muscle, two of the most insulin-responsive tissues. The nucleotide and deduced amino acid sequences of PHAS-I differ from any that have been reported, and homology screening provided no clues concerning the function of the protein. However, in view of its tissue distribution and the fact that the protein is phosphorylated in response to insulin, we speculate that PHAS-I is important in insulin action.
Hu
C
C
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110.
Pang
S
S
Kong
X
X
Velleca
M
M
Lawrence
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D006133:Growth Substances / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C499526:Eif4ebp1 protein, rat; D006133:Growth Substances; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger