Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tyrosine protein kinase present in the membrane fraction of bovine cerebral cortex were extracted and chromatographically fractionated. The activity associated with tyrosine protein kinases was fully extracted from the membranes by 1% sodium cholate and eluted in two peaks (I and II) during chromatography of protein extracts on DEAE-Toyopearl in the presence of sodium cholate. The predominant in cerebral cortex membrane tyrosine protein kinase of peak I (about 75% of the total activity) was purified 1930-fold by gel filtration on Sephacryl S-300, chromatography on hexyl- and phenyl-Sepharose and by rechromatography on DEAE-Toyopearl. The amount of the enzyme prepared from 250 g of bovine brain was 20 micrograms, the enzyme yield and specific activity being 3.8% and 3.9 nmol/mg protein/min, respectively. The purified protein kinase of peak I represents a protein with Mr of 62-63,000 (p62) capable of being autophosphorylated in the presence of [gamma-32P]. Protein kinase p62 phosphorylates enolase, tubulin and calpactin I as well as model substrates in the series: histone H5 greater than poly(G, T)n greater than or equal to histone H2A greater than poly(G, A, T)n, histone H4 greater than caseins, histones H1 and H2B, poly(G, A, L, T)n. The enzyme is specific for Mn2+ at the optimal concentration about 1 mM. The KmMn-ATP is 0.3 microM; Km for histone H5 and poly(G, T)n are 0.45 mg/ml and 0.06 mg/ml, respectively. The protein kinase p62 activity is inhibited by NaCl (IC50 approximately 75-100 mM) as well as by quercetin, adriamycin and lasalocid (IC50 approximately 14-34, 23 and 90 microM, respectively). It is concluded that protein kinase p62 is analogous to the c-src gene protein kinase.
 ...
PMID:[Tyrosine protein kinase from cattle cerebral cortex: purification, characteristics, protein substrates for phosphorylation and inhibitors of activity]. 180 85

Tyrosine protein kinases (TPKs) have been implicated in mitotic signalling in a wide range of cells including lymphocytes. We describe here the partial characterization of a heat stable TPK inhibitor from both normal and malignant human lymphoid cells. Inhibitory activity was not attributable to contaminating ATPase, protease or phosphatase activities or to the Ca2+-binding protein S100. Preparations of the TPK inhibitor did not reduce the activity of cAMP-dependent protein kinase. While the inhibitor decreased the activity of TPKs towards an exogenous peptide substrate, it did not affect the autophosphorylation of microsomal TPKs. These results raise the possibility that the activity of TPKs in lymphoid cells may be regulated by an inhibitor protein.
 ...
PMID:An endogenous inhibitor of the protein tyrosine kinase activity of normal and malignant human lymphoid cells. 252 67

Colonic epithelial cell injury is the common manifestation of inflammatory diseases of the bowel. One form of epithelial injury is apoptosis. In our study, we investigated the mechanism leading to apoptosis in HT-29 cells in response to TNF-alpha and ligation of Fas Ag. HT-29 displayed a dual response to TNF-alpha and Fas Ag ligation: in combination with IFN-gamma, HT-29 cells underwent apoptosis, whereas independently, these factors stimulated secretion of IL-8. We used this model of immune-mediated epithelial cell injury to elucidate the signals leading to apoptosis in response to TNF-alpha and Fas Ag ligation compared with the signals leading to induction of IL-8 secretion. The model was further used to distinguish signaling differences between TNF-alpha receptors and the Fas Ag in this cell line. The experiments presented here demonstrate that Fas Ag ligation alone led to production of IL-8 by colonic epithelial cells and represented another function mediated by Fas Ag in addition to apoptosis. This study shows that the pathways leading to cell death and IL-8 production in response to Fas Ag ligation and TNF-alpha were similar with regard to their requirements for new gene expression, protein synthesis, and protein kinase activity. Specifically, new gene expression and protein synthesis were not necessary for TNF-alpha- and Fas Ag-mediated apoptosis, but were necessary for TNF-alpha- and Fas Ag-mediated IL-8 secretion. Tyrosine protein kinase phosphorylation was necessary to signal secretion of IL-8 in response to both agonists but it was not necessary for apoptosis. In spite of the similarities between these two agonists, the kinetics of apoptosis via Fas Ag were significantly more rapid than through the TNF-alpha receptor and serve to distinguish these two signals.
 ...
PMID:Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen. 759 69

Tyrosine protein kinases (TPKs) represent a diverse group of enzymes that contribute to cellular signal transduction. The generally low abundance of TPKs, coupled with their rapid activation and deactivation, usually precludes their purification through conventional biochemical means. Using immune-complex protein kinase assays, the presence or absence of a given TPK can be established and an estimation of its functional state obtained. In the Basic Protocol of this unit, TPKs are immunoprecipitated, allowed to autophosphorylate in the presence of labeled ATP, run out on an SDS-PAGE gel, and detected by autoradiography. Alternate protocols are provided for the assessment of the functional state of TPKs by providing a potential substrate along with the labeled ATP in the reaction mixture. In the first alternate protocol, the exogenous substrate is a protein, permitting simultaneous assessment of autophosphorylation and exogenous substrate phosphorylation. The second alternate protocol utilizes a peptide substrate, resulting in a rapid, high-throughput assay that evaluates only exogenous substrate phosphorylation.
 ...
PMID:Immune-complex assays for tyrosine protein kinases. 1843 5