Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When rat mast cells are prelabeled with 32PO4 and exposed to non-immunologic or immunologic stimuli under conditions that lead to mediator release from granules, they show rapid increases in labeling of a number of high molecular weight proteins. To determine if granule membrane proteins are subject to protein phosphorylation and perhaps participate in this response, granules with intact or broken membranes were isolated from sonicated, purified rat serosal mast cells on a Percoll gradient. When the granules with broken membranes were incubated with [gamma-32P]ATP and Mg2+ in the absence of exogenous protein kinases, one major radioactive band was recovered in the 44K area after electrophoresis in sodium dodecyl sulfate/polyacrylamide gels. The phosphorylation reaction with ATP required Mg2+, was enhanced by 0.05 to 0.5 microM cyclic AMP, and was inhibited by Ca2+ (0.5 mM and higher). The initial reaction was rapid, and the maximal response was seen at 30 degrees. The 44K band was absent in granules with intact membranes incubated with [gamma-32P]ATP but present when intact granules were lysed with distilled water before adding the [gamma-32P]ATP. These observations indicate that granules have an endogenous phosphorylating system and that the phosphorylation response is on the inner surface of the granule membranes. The possibility was not excluded that a portion of the phosphorylating activity was derived from the cytosol and became firmly associated with broken granules when the intact cells were sonicated. Analysis for possible phosphorylated amino acids in the 44K band after acid hydrolysis showed both phosphoserine and phosphothreonine, indicating that the radioactivity was in a phosphorylated protein or glycoprotein. The 44K phosphorylated protein was made up of several components ranging in pI from approximately 7.6 to 6.6. While the identity of the phosphorylated 44K polypeptide is uncertain, one important possibility is that it is part of an autophosphorylated cAMP dependent protein kinase. The cyclic AMP dependent phosphorylating activity present in granules provides a mechanism by which the granules might respond rapidly to cyclic AMP during mediator release.
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PMID:Protein phosphorylation in rat mast cell granules. Cyclic AMP dependent phosphorylation of a 44K protein associated with broken granules. 302 1

The insulin receptor possesses protein kinase activity, which may play a role in mediating insulin action. Recently, we have identified a glycoprotein (pp120) in rat liver plasma membranes that is phosphorylated by the solubilized insulin receptor in a cell-free system. We now report that insulin stimulates phosphorylation of pp120 in intact H-35 cells. H-35 cells were preloaded with [32P]orthophosphate to label the intracellular ATP pool. Insulin caused a 10-fold increase in the phosphorylation of its receptor and a 2-fold increase in phosphorylation of pp120 (P less than 0.001). The time course of insulin's stimulation of pp120 closely paralleled that of insulin receptor phosphorylation over the time period investigated (15-45 min). This effect had the specificity corresponding to the insulin receptor. Epidermal growth factor was inactive, and insulin-like growth factor I had approximately equal to 1% the potency of insulin in this regard. Insulin increased 32P incorporation into pp120 in a linkage that was stable to alkaline hydrolysis, as would be expected for tyrosine-specific phosphorylation. Direct phosphoamino acid analysis confirmed that insulin increased 32P incorporation into phosphotyrosine residues in pp120.
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PMID:Insulin stimulates phosphorylation of a 120-kDa glycoprotein substrate (pp120) for the receptor-associated protein kinase in intact H-35 hepatoma cells. 303 36

A 107 kDa (pp107) casein kinase G (ck-G) substrate has been purified from mouse and beef thyroid cytosol; ck-G was purified from beef thyroid cytosol. Ck-G and pp107 were found to co-elute on DEAE cellulose chromatography at approximately 300 mM NaCl. Ck-G and pp107 were separated by spermine-agarose affinity chromatography; pp107 is eluted with a stepped gradient at 250 mM NaCl and ck-G is eluted at 500 mM NaCl. Ck-G was subsequently purified by casein-agarose and GTP-agarose affinity chromatography. The 107 kDa protein was purified using heparin-agarose affinity chromatography. Phosphorylation of purified pp107 by ck-G was stimulated by spermine (ED50 = 0.2 mM) and inhibited by low concentrations of heparin (0.1-5 micrograms/ml). The Km and Vmax for the reaction were 1.46 microM and 32.2 nmoles P transferred/20 min/mg protein, respectively; 1 mole pp107 incorporated 0.81 mole phosphorus. pp107 was found to be an acidic substrate with a pI of 3.87 and was absorbed to wheat-germ agglutinin-agarose. The specificity of pp107 phosphorylation was studied using diacylglycerol-activated calcium/phospholipid-dependent protein kinase C, calcium-activated calmodulin-dependent protein kinase, and the catalytic subunit of cAMP-dependent protein kinase A. Phosphorylation of pp107 by the other protein kinases tested never exceeded 4% of that of ck-G. Our data show that pp107 is an acidic glycoprotein which may serve as a high-affinity and specific substrate for ck-G.
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PMID:Purification of a 107 kilodalton (kDa) casein kinase G substrate from thyroid cytosol. 320 Feb 52

1. Triton extracts of syncytiotrophoblast membranes were incubated with [gamma-32P]ATP, MgCl2 and MnCl2. Addition of epidermal growth factor (EGF) resulted in increased phosphorylation not only of the EGF receptor and a Mr-35,000 protein as previously described, but also a protein of Mr 95,000 on both tyrosine and serine residues. In addition, a small increase in the phosphorylation of a protein of Mr 105,000 was observed. Spermine had a similar effect on the phosphorylation of the Mr-95,000 protein, without affecting the phosphorylation of the other proteins. In the absence of MnCl2, the effect of spermine on the phosphorylation of Mr-95,000 protein was still evident, whereas that of EGF was greatly diminished. 2. The Mr-95,000 protein bound poorly to wheat-germ-lectin-Sepharose and was not precipitated by antisera specific for insulin and EGF receptors. The protein continued to exhibit serine and tyrosine phosphorylation on addition of [gamma-32P]ATP, MgCl2 and MnCl2 to a glycoprotein-depleted fraction prepared by chromatography on wheat-germ-lectin-Sepharose. The extent of phosphorylation was no longer increased by spermine or EGF, but was inhibited by heparin. 3. It is suggested that the Mr-95,000 protein not only is a possible direct substrate for the EGF-receptor (but not the insulin receptor) tyrosine kinase but is a substrate for other endogenous kinases, including a protein tyrosine kinase which is probably not a glycoprotein, and a protein serine kinase with properties similar to those of casein kinase II.
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PMID:Epidermal growth factor, but not insulin, stimulates tyrosine phosphorylation of an endogenous protein of Mr 95,000 in triton extracts of human placental syncytiotrophoblast membranes. 332 13

Avian leukemia virus S13 induces erythroblastosis, granulocytic leukemia, fibrosarcoma, anemia, and endothelial neoplasia. It transforms chick embryo fibroblasts and primitive erythroid cells in culture and is defective in replication. Its onc gene, sea, is expressed as transformation specific env-sea fusion glycoprotein of 155 kDa. Gp155 is proteolytically processed into gp85env and gp70env-sea. The latter shows tyrosine specific protein kinase activity. Avian sarcoma virus 17 induces fibrosarcoma and transforms chick embryo fibroblasts in culture. Its cell derived onc gene, jun, is not related to known onc genes and appears to be expressed as a gag-jun fusion protein of 55 kDa. The amino acid sequence of jun shows homology in its C-terminal region to the C-terminal DNA binding region of the yeast regulatory protein GCN4, suggesting that the jun protein may bind to DNA.
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PMID:Two new retroviral onc genes, sea and jun. 333 12

The primary structure of the beta chain of human glycoprotein Ib (GPIb), the platelet receptor for von Willebrand factor, has been established by a combination of cDNA cloning and amino acid sequence analysis. A lambda phage cDNA expression library prepared from human erythroleukemia cells (HEL cells) was screened with a radiolabeled affinity-purified rabbit polyclonal antibody to the beta chain of GPIb. Eighteen positive clones were isolated and plaque-purified and the nucleotide sequences of three were determined. The composite sequence spanned 968 nucleotides and included a 5' untranslated region of 22 nucleotides, an open reading frame of 618 nucleotides encoding a signal peptide of 28 amino acids and a mature protein of 181 amino acids, a stop codon, and a 3' noncoding region of 307 nucleotides. The 3' noncoding sequence also contained a polyadenylylation signal (AATAAA) 14 nucleotides upstream from the poly(A) tail of 18 nucleotides. Edman degradation of the intact beta chain and of peptides produced by chemical cleavage yielded amino acid sequences spanning 76 residues that were identical to those predicted from the cDNA. The amino-terminal region of the beta chain contains a leucine-rich sequence of 24 amino acids that is similar to a sequence that occurs as seven tandem repeats in the alpha chain of GPIb and nine tandem repeats in leucine-rich alpha 2-glycoprotein. The leucine-rich sequence in the beta chain of GPIb is flanked on both sides by amino acid sequences that are similar to those flanking the leucine-rich tandem repeats of the alpha chain of GPIb and leucine-rich alpha 2-glycoprotein. The amino-terminal region of the beta chain of GPIb is followed by a transmembrane segment of 25 amino acids and an intracellular segment of 34 amino acids at the carboxyl terminus of the protein. The intracellular segment contains an unpaired cysteine and two potential sites for phosphorylation by cAMP-dependent protein kinase.
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PMID:The alpha and beta chains of human platelet glycoprotein Ib are both transmembrane proteins containing a leucine-rich amino acid sequence. 335 70

Drug-resistant cell lines derived from the mouse macrophage-like cell line J774.2 express the multidrug resistance phenotype which includes the overexpression of a membrane glycoprotein (130-140 kilodaltons). Phosphorylation of this resistant-specific glycoprotein (P-glycoprotein) in intact cells and in cell-free membrane fractions has been studied. The phosphorylated glycoprotein can be immunoprecipitated by a rabbit polyclonal antibody specific for the glycoprotein. Phosphorylation studies done with partially purified membrane fractions derived from colchicine-resistant cells indicated that (a) phosphorylation of the glycoprotein in 1 mM MgCl2 was enhanced a minimum of 2-fold by 10 microM cAMP and (b) the purified catalytic subunit of the cAMP-dependent protein kinase (protein kinase A) phosphorylated partially purified glycoprotein that was not phosphorylated by [gamma-32P]ATP alone, suggesting that autophosphorylation was not involved. These results indicate that the glycoprotein is a phosphoprotein and that at least one of the kinases responsible for its phosphorylation is a membrane-associated protein kinase A. The state of phosphorylation of the glycoprotein, which is a major component of the multidrug resistance phenotype, may be related to the role of the glycoprotein in maintaining drug resistance.
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PMID:Phosphorylation of the multidrug resistance associated glycoprotein. 342 52

Phosphorylation of secretory proteins is an uncommon event. In this manuscript, the phosphorylation of human chorionic gonadotropin, a glycoprotein hormone secreted by the JAR choriocarcinoma cell line, is described. Labeling of JAR cells with 32PO4 indicates that both the intracellular and the secreted forms of the free alpha subunit are phosphorylated. Although the secreted alpha beta dimer also incorporates 32PO4, there is little detectable phosphorylation of the intracellular precursors of alpha beta dimer, suggesting that dimer phosphorylation occurs as a late event in post-translational processing. In addition, phorbol 12-myristate 13-acetate markedly stimulates the phosphorylation of both intracellular and secreted forms of free alpha subunit and to a lesser extent of secreted alpha beta dimer. In vitro assays, using homogenates of JAR cells as a source of protein kinase activity, indicate that the uncombined alpha subunit is preferentially phosphorylated. The phosphorylation sites are on serine and threonine residues in the alpha subunit.
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PMID:Phosphorylation of the secreted, free alpha subunit of human chorionic gonadotropin. 346 19

Multiple kinases interact at the multicomponent murine T cell antigen receptor. Antigen induces serine phosphorylation of the 21-kDa gamma glycoprotein and tyrosine phosphorylation of p21, a distinct 21-kDa chain. We demonstrate that tyrosine phosphorylation is due to kinase activation, and that all phosphorylated p21 is associated with the antigen receptor. We also show that antigen leads to polyphosphoinositide metabolism and subsequent protein kinase C activation. The two phosphorylation events can be dissociated by protein kinase C depletion, which eliminates phorbol 12-myristate 13-acetate-induced serine but not tyrosine phosphorylation. Activation of a third kinase, cyclic AMP-dependent protein kinase, inhibits both serine and tyrosine events, yet this inhibition can be modulated by addition of the protein kinase C activator, phorbol 12-myristate 13-acetate. Receptor-mediated signal transduction may be understood as the interaction of multiple stimulatory and inhibitory kinase activities.
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PMID:Multiple kinases and signal transduction. Phosphorylation of the T cell antigen receptor complex. 349 29

The receptors for insulin and epidermal growth factor possess tyrosine-specific protein kinase activity which may play a role in mediating the biological actions of these two peptides. We have identified a 120 kDa glycoprotein (pp120) in rat liver plasma membranes which can be phosphorylated by the insulin receptor in a cell-free system and in intact cultured hepatoma cells. In the present report, we have demonstrated in a cell-free system that solubilized epidermal growth factor receptors can phosphorylate tyrosine residues in pp120.
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PMID:Rat liver membranes contain a 120 kDa glycoprotein which serves as a substrate for the tyrosine kinases of the receptors for insulin and epidermal growth factor. 354 68


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