A calcium-dependent 35-kilodalton substrate for epidermal growth factor receptor/kinase isolated from normal tissue.
We have previously reported the isolation of a 35-kDa protein from A-431 cells that, in the presence of Ca2+, can serve as a substrate for the epidermal growth factor (EGF) receptor/tyrosine kinase (Fava, R.A., and Cohen, S. (1984) J. Biol. Chem. 259, 2636-2645). We now report the detection of an antigenically related 35-kDa protein in a number, but not all, of rat, pig, and human tissues. These antigenically related proteins also can serve as substrates for the EGF receptor/kinase in the presence of Ca2+. All of these proteins share the property of reversible, Ca2+-dependent binding to the particulate fraction (presumably membranes) of cell homogenates. We have isolated the 35-kDa substrate from porcine lung and have demonstrated that it is a Ca2+-binding protein. The amino-terminal sequence and the site of tyrosine phosphorylation therein have been determined. The positions of the acidic amino acid residues amino-terminal to the tyrosine phosphorylation site bear a distinct resemblance to the sequence in the homologous region of a number of other substrates for tyrosine kinases. Based on available data, the 35-kDa protein clearly differs from the protein I complex derived from intestinal mucosa and thought to be related to the proteins isolated herein (Gerke, V., and Weber, K. (1985) J. Biol. Chem. 260, 1688-1695). Finally, we report a striking sequence homology between the porcine 35-kDa described herein and human lipocortin, a phospholipase A2 inhibitor.
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism; D002460:Cell Line; D004533:Egtazic Acid / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008970:Molecular Weight; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine; D014018:Tissue Distribution
D002135:Calcium-Binding Proteins; D004533:Egtazic Acid; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D002118:Calcium