Inositol phospholipid-specific phospholipase C: complete cDNA and protein sequences and sequence homology to tyrosine kinase-related oncogene products.
Antibodies against an inositol phospholipid-specific phospholipase C purified from bovine brain were used to screen rat brain lambda gt11 expression cDNA libraries. Complete sequences of three cDNA inserts yielded a cumulative sequence of 5106 base pairs. The deduced protein had 1289 amino acids with a calculated molecular weight of 148,431. The determination of an open reading frame was aided by the amino acid sequences of 21 tryptic peptides isolated from bovine brain phospholipase C. Only 9 residues of a total of 140 amino acid residues determined for the bovine enzyme were different from those deduced from the rat cDNA. Two regions of phospholipase C (amino acid residues 555-598 and 668-705) exhibited significant amino acid similarities to the products of various tyrosine kinase-related oncogenes (yes, src, fgr, abl, fps, fes, and tck). The homologous domain was located in the region that is not essential for the protein-tyrosine kinase activity but is likely to be involved in an interaction with cellular components that modulate kinase function. Therefore, this unexpected similarity raises the possibility that the 148-kDa phospholipase C and cytoplasmic tyrosine kinases are modulated by common cellular component(s).
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Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D002417:Cattle; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D015246:Deoxyribonuclease EcoRI; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics; D009857:Oncogenes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism
D009856:Oncogene Proteins, Viral; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D004247:DNA; D011505:Protein-Tyrosine Kinases; D004262:DNA Restriction Enzymes; D015246:Deoxyribonuclease EcoRI; D010738:Type C Phospholipases