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)

A nonhistone chromatin protein (NHCP) has been purified to homogeneity from a 0.5 M NaCl extract of Ehrlich ascites tumor cell (EAT cell) nuclei as a phosphate acceptor for casein kinase II using ion-exchange column chromatographies and Sephacryl S300 gel filtration. The purified NHCP (approximate Mr = 400,000) was found to be a tetramer of an Mr = 98,000 polypeptide (pI = 6.9) and to have high contents of glycine (15%) and serine (11.6%). This protein (designated as 400-kDa NHCP) was highly phosphorylated by casein kinase II (Mr = 130,000), but not by histone kinase. Casein kinase II phosphorylated only seryl residues of the purified 400-kDa NHCP. The NHCP bound with DNA, but not with RNAs, and the DNA binding ability of the protein was reduced when it was phosphorylated by casein kinase II. Moreover, we found that (a) the 400-kDa NHCP is present in large quantities in malignant mouse cells, such as EAT, EL-4, and Meth-A cells, but only slightly in normal tissues and cells; (b) the protein level is rapidly increased when mouse lymphocytes are treated with recombinant interleukin 2 (T cell growth factor) or concanavalin A; and (c) the kinase responsible for the 400-kDa NHCP phosphorylation in the chromatin of various mouse cells is a casein kinase II. These experimental results suggest that the 400-kDa NHCP acts as an effective phosphate acceptor for casein kinase II at the chromatin level and that an increased phosphorylation of the protein by the kinase may be implicated in the progress of cell differentiation and proliferation.
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PMID:Purification and characterization of a 400-kDa nonhistone chromatin protein that serves as an effective phosphate acceptor for casein kinase II from Ehrlich ascites tumor cells. 317 May 22

We found that K252a, a potent inhibitor of protein kinases (PK), induced DNA re-replication of Meth-A cells, i.e., DNA synthesis at a higher DNA ploidy without undergoing cytokinesis (polyploidization). The K252a-induced polyploidization was inhibited by phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, suggesting that the polyploidization is caused through inhibition of PKC. By contrast, the polyploidization was potentiated by adenosine 3':5'-cyclic monophosphate (cAMP), a cAMP-dependent protein kinase (PKA) activator. These findings suggest that the cAMP-dependent signaling pathway and diacylglycerol (DAG)-dependent signaling pathway play an important role in regulating the induction of polyploidization in Meth-A cells, through a possible "cross-talk" between the two pathways.
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PMID:Potentiation of K252a, a protein kinase inhibitor-induced polyploidization by cAMP in cultured fibrosarcoma cell line. 799 7

Exponentially growing Meth-A cells expressing H-2K(d).D (d) antigen were found to induce alopecia when injected intraperitoneally into normal C57BL/6 mice, which express the H-2K(b).D (b) antigen. However, the capacity to induce alopecia disappeared when Meth-A cells were treated with K252a, which inhibits protein kinases. Histologically, skin in affected areas showed dense mononuclear cell infiltration and a focal foreign-body giant-cell reaction in hair follicles. The subtyping of lymphocytes in peripheral blood demonstrated a significant difference between normal mice and Meth-A cell-injected mice. To further examine the mechanism by which the alloantigen induces alopecia, lymphocytes isolated from the peripheral blood of normal C57BL/6 mice were cultured in medium containing Meth-A cell homogenate, phytohemagglutinin (PHA) and recombinant mouse interleukin-2 (rm IL-2), and intravenously injected into normal C57BL/6 mice. The adoptive transfer of the lymphocytes induced alopecia in a similar way. These findings suggest that the protein kinase-modulated alloantigen induces alopecia by disturbing the immunological homeostasis, and that lymphokine-activated killer cells play an important role in induction of alopecia by cross-reacting with hair follicles.
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PMID:Autoimmune hair loss induced by alloantigen in C57BL/6 mice. 1265 55

Using computer-assisted microscopic image analysis, we have found that algal yessotoxin (YTX) affects the immune response of Mytilus galloprovincialis. Indeed, YTX increases immunocyte cell motility through the involvement of both extracellular Ca2+ and cAMP, but not through protein kinase A, protein kinase C or phosphoinositide 3-kinase. Alone, however, the toxin does not induce any effect, as its action on cell motility is observed only after addition of the chemotactic substance N-formyl-Meth-Leu-Phe (fMLP). fMLP is known to induce cellular changes via both the phosphatidylinositol and cAMP pathways and, from this scenario, we can surmise that Ca2+ and cAMP concentrations rise sufficiently in fMLP-activated immunocytes to reveal YTX action. One possible explanation is that the toxin increases fMLP-mediated cell activation by intervening in L-type Ca2+-channel opening through a cAMP-dependent/PKA-independent pathway.
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PMID:Yessotoxin affects fMLP-induced cell shape changes inMytilus galloprovincialis immunocytes. 1475 69

Aspirin displays, at millimolar concentrations, several mechanisms independent from its ability to inhibit cyclooxygenases. Occasionally, the mechanisms displayed in vitro have been clearly related to an effect of clinical relevance in vivo. An expanding literature has been focusing on the cytoprotective effect of aspirin in neurodegenerative disorders and the activation of AKT pathway in neuroprotection and induction of resistance to anticancer drugs. In this work, we tested the ability of aspirin to activate the AKT survival pathway in methylcholanthrene-induced fibrosarcoma cells (Meth A) transplanted into BALB/c nude mice and the clinical effect of aspirin cotreatment during etoposide (VP-16)-based anticancer therapy. We found that cotreatment with aspirin reduced VP-16-induced apoptosis and activated AKT in vitro and in vivo. In Meth A-bearing mice, aspirin administration also activated glycogen synthase kinase-3 and reduced the activity and the efficacy of anticancer therapy in VP-16 cotreated animals. Our data suggest that the antiapoptotic effect of aspirin operates in vivo through the activation of AKT-glycogen synthase kinase pathway causing a decrease in the outcome of VP-16-based therapy. These findings could have clinical relevance in treatment of human malignancies.
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PMID:Aspirin reduces the outcome of anticancer therapy in Meth A-bearing mice through activation of AKT-glycogen synthase kinase signaling. 1673 65