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Regulation of the oncogenic activity of the cellular src protein requires the correct spacing between the kinase domain and the C-terminal phosphorylated tyrosine (Tyr-527). 下载免费PDF全文
Repression of the tyrosine kinase activity of the cellular src protein (pp60c-src) depends on the phosphorylation of a tyrosine residue (Tyr-527) near the carboxy terminus. Tyr-527 is located 11 residues C terminal from the genetically defined end of the kinase domain (Leu-516) and is therefore in a negative regulatory region. Because the precise sequence of amino acids surrounding Tyr-527 appears to be unimportant for regulation, we hypothesized that the conformational constraints induced by phosphorylated Tyr-527 may require the correct spacing between the kinase domain (Leu-516) and Tyr-527. In this report, we show that deletions at residue 518 of two, four, or seven amino acids or insertions at this residue of two or four amino acids activated the kinase activity and thus the transforming potential of pp60c-src. As is the case for the prototype transforming variant, pp60527F, activation caused by these deletions or insertions was abolished when Tyr-416 (the autophosphorylation site) was changed to phenylalanine. In comparison with wild-type pp60c-src, the src proteins containing the alterations at residue 518 showed a lower phosphorylation state at Tyr-527 regardless of whether residue 416 was a tyrosine or a phenylalanine. Mechanisms dealing with the importance of spacing between the kinase domain and Tyr-527 are discussed. 相似文献
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The primary structures of the alpha chains in hemoglobins from three stocks of mice with theHba
w2,Hba
w3, andHba
w4 haplotypes were determined to establish whether the tentative alpha-chain assignments based on the results of isoelectric focusing patterns were correct. TheseHba haplotypes were identified in laboratory descendants of feral mice captured in different parts of the world. Hemoglobin from Centreville, Maryland,Mus musculus domesticus (Hba
w2) contains equal amounts of alpha chains 1 and 3. Hemoglobin from CzechMus musculus musculus (Hba
w4) contains equal amounts of alpha chains 3 and 4. Amino acid analysis of the alpha-globins of Skive DanishMus musculus musculus (Hba
w3) establishes that its hemoglobin is comprised of about one-third alpha chain 2 as expected plus a greater amount of a unique alpha chain that has not been described previously. This unique alpha chain has glycine at position 25, isoleucine at position 62, and serine at position 68; it is called chain 7. It may represent an intermediate in the evolution of genes that code for chain 2 (which has glycine, valine, and serine at positions 25, 62, and 68, respectively) and chain 4 (which has valine, isoleucine, and serine at positions 25, 62, and 62, respectively).This research was sponsored jointly by the National Institutes of Environmental Health Sciences under Contract 1-ES-55078 and by the Office of Health and Environmental Research, U.S. Department of Energy, under Contract DE-AC05-840R21400 with Martin Marietta Energy Systems, Inc. 相似文献
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M H Cobb J G Burr M E Linder T B Gray J S Gregory 《Biochemical and biophysical research communications》1986,137(2):702-708
Insulin and transformation by Rous sarcoma virus stimulate the phosphorylation of ribosomal protein S6. Soluble fractions containing activated S6 protein kinase from insulin-treated cells and from transformed chick embryo fibroblasts were compared. Based upon several characteristics notably elution from DEAE-cellulose and sedimentation in glycerol gradients, these two S6 protein kinase activities appear to be similar enzymes. Thus insulin and retroviral transformation may activate the same enzyme to regulate the phosphorylation state of S6. 相似文献
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H Owaki R Makar T G Boulton M H Cobb T D Geppert 《Biochemical and biophysical research communications》1992,182(3):1416-1422
Extracellular signal-regulated kinases 1 and 2 are growth factor-sensitive serine/threonine kinases. cDNAs for both human kinases were isolated and sequenced. The nucleic acid and deduced protein sequences of human extracellular signal-regulated kinase 1 were 88% and 96% identical, respectively, to the homologous rat sequences. The nucleic acid and deduced protein sequences of human extracellular signal-regulated kinase 2 were 90% and 98% identical, respectively, to the corresponding rat sequences. A human extracellular signal-regulated kinase 2 specific probe was used to demonstrate that the mRNA for this kinase was present in T cells and did not change with activation. The deduced protein sequences of both human kinases were greater than 95% identical to two Xenopus kinase sequences, indicating that these enzymes are highly conserved across species. 相似文献
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M. Cobb 《Genetics》1996,144(4):1577-1587
Two Drosophila melanogaster third chromosomes carrying the EMS-induced mutations IndifferentA (IndfA) and IndifferentB (IndfB), previously isolated from larvae showing an anosmia when stimulated with nonanol, were recombined with a multi-marked chromosome in order to localize the mutant character(s). Recombinant strains were tested for their larval olfactory responses and classed as either mutant or wild type; both Indf characters were found to be located on the right arm of the chromosome, between ebony and claret. Deletion mapping suggests that the Indifferent wild-type character is a haplo-insufficiency and that IndfA and IndfB are located in cytological region 96A2-7. Deficiencies and both mutant strains were tested with 14 closely related odors (alcohols, acetates, acids and methyl esters, between eight and 10 carbons long). When stimulated with methyl octanoate, IndfA and IndfB appeared recessive; noncomplementation was observed for this phenotype in IndfA/IndfB hybrids indicating that the two characters are allelic. The overall responses of IndfA, IndfB and the deficiencies indicate that Indf is involved in processing organic odors of between eight and 10 carbons in length. 相似文献