Control of src kinase activity by activators, inhibitors, and substrate chaperones.
The activities of src tyrosine kinases are greatly influenced by substrate modulators (chaperones). In the presence of bovine serum albumin, the phosphorylation of a random polymer of glutamic acid, alanine, and tyrosine (1:1:1) by src kinases is stimulated 20- to 100-fold, but there is little stimulation with a polymer of glutamic acid and tyrosine (4:1) as substrate. This suggests that serum albumin interacts with the substrates rather than with the enzyme. groEL and several other heat shock proteins also stimulate the phosphorylation of a random polymer of glutamic acid, alanine, and tyrosine (1:1:1). In the absence of substrate modulators, the phosphorylation of calmodulin and of several ras proteins by src kinase is barely detectable. In the presence of polylysine or protamine, marked phosphorylation is observed. Another type of control of src kinase activities appears to be directed toward the enzyme rather than the substrate. Triton X-100 extracts of plasma membranes of bovine brain contain a heat-stable factor that stimulates c-src kinase activity with any of the polymers as substrate. The same extract contains a heat-labile factor that preferentially inhibits c-src kinase activity. The two factors are separated by DEAE-Sephacel and phosphocellulose chromatography. The presence of the activator enhances the potency of the inhibitor.
Abdel-Ghany
M
M
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853.
el-Gendy
K
K
Zhang
S
S
Racker
E
E
D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D007304:Insect Viruses / Q000235:genetics; D007313:Insecta; D007700:Kinetics; D008565:Membrane Proteins / Q000302:isolation & purification / Q000494:pharmacology; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection
D008565:Membrane Proteins; D010455:Peptides; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)