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)

We have investigated the effect of 12-O-tetradecanoylphorbol 13-acetate (TPA) on the synthesis and modification of polypeptides in normal avian cells and cells infected by wild-type and temperature-sensitive Rous sarcoma virus (RSV). Using two-dimensional gel electrophoresis, we have detected alterations in both the abundance of cellular polypeptides and in their phosphorylation that seem unique to TPA treatment. However, the state of phosphorylation of the major putative substrate for the action of the src gene-associated protein kinase, the 34- to 36-kilodalton protein, was not altered. Moreover, examination of the phosphorylated amino acid content of total cellular phosphoproteins revealed that the response to TPA was not associated with detectable increases in their phosphotyrosine content. These results make it unlikely that TPA acts by the activation of the phosphorylating activity of the cellular proto-src gene or by the activation of other cellular phosphotyrosine-specific kinases. We have shown previously that temperature-sensitive RSV-infected cells at nonpermissive temperature demonstrate an increased sensitivity to TPA treatment [Bissell, M. J., Hatie, C. & Calvin, M. (1979) Proc. Natl. Acad. Sci. USA 76, 348-352]. Our present results indicate that this is not due to reactivation of the phosphorylating activity of the defective src gene product or to its leakiness, and they lend support to the notion of multistep viral carcinogenesis.
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PMID:Tumor promoters alter gene expression and protein phosphorylation in avian cells in culture. 617 14

Several kinds of virus can cause cancer. The various viruses with oncogenic potential probably act through different mechanisms and depend on different host factors. The tumour viruses with small genomes are best understood and may be regarded as transposable genetic elements. By integrating into host cell chromosomal DNA, they may cause mutations and chromosomal rearrangements that predispose to cancer. The insertion of viral promoter sequences adjacent to certain host genes can lead to ectopic gene expression resulting in neoplasia. There is growing evidence, however, that the most strongly oncogenic strains of small DNA and RNA viruses carry 'oncogenes' that encode 'transforming' proteins. Papovavirus early proteins interact with cellular proteins involved in the control of cell proliferation. Many, but not all, of the transforming proteins of retroviruses are located at the plasma membrane and exhibit protein kinase activity, phosphorylating tyrosine residues. Most of the oncogenes of retroviruses studied so far are derived from cellular genes which may play important roles in regulating normal cell proliferation and differentiation. Retrovirus oncogenes may therefore be regarded as kidnapped host factors placed under the control of infectiously transmitted promoter elements. A variety of other host factors and exogenous cofactors affect the course of viral carcinogenesis, from influencing initial infection to immunological responses to chronic infection. Lastly, the endogenous viral genomes, which are inherited as host genetic elements, should themselves be considered as host factors that interact with exogenous carcinogens such as chemicals and ionizing radiation.
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PMID:Viral mechanisms of carcinogenesis. 689 72

Efforts to clarify the mechanisms of viral carcinogenesis have been hampered, no doubt, by the lack of understanding of the complex gene-regulatory processes in the eukaryotic genome. However, numerous investigators have produced enlightening information concerning potential gene-regulatory, nuclear phosphorylation reactions. In addition, equally interesting studies involving transforming viruses have revealed that some viral products responsible for transformation have an associated protein kinase activity. These similar biochemical processes may suggest how some transforming viruses could subvert normal gene-regulatory processes.
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PMID:Hypothesis: is viral transformation mediated by alterations in chromosomal proteins? 689 31

Three separate experimental approaches, using site-selective cAMP analogs, antisense strategy and retroviral vector-mediated gene transfer, have provided evidence that two isoforms, the RI- and RII-regulatory subunits of cAMP-dependent protein kinase, have opposite roles in cell growth and differentiation; RI being growth stimulatory while RII is a growth-inhibitory and differentiation-inducing protein. As RI expression is enhanced during chemical or viral carcinogenesis, in human cancer cell lines and in primary human tumors, it is a target for cancer diagnosis and therapy. 8-Cl-cAMP and RI antisense oligodeoxynucleotide, those that effectively down-regulate RI alpha and up-regulate RII beta, provide new approaches toward the treatment of cancer. This approach to modulation of RI vs RII cAMP transducers may also be beneficial toward therapy of endocrine or cellular dysfunction-related diseases where abnormal signal transduction of cAMP is critically involved.
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PMID:The regulatory subunit of cAMP-dependent protein kinase as a target for chemotherapy of cancer and other cellular dysfunctional-related diseases. 802 60