Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of fractionated doses of Co(60) gamma-irradiation (2 Gy per fraction over 5 days), as is delivered in cancer radiotherapy, was compared with acute doses of 10 and 2 Gy, in a serially transplanted mouse fibrosarcoma grown in Swiss mice. The aspects that were studied included the three major mitogen-activated protein (MAP) kinases, namely p44 MAP kinase, p38 MAP kinase, and stress-activated protein (SAP) kinase, which are known to be involved in determining the cell fate following exposure to ionizing radiation. The response of dual specificity phosphatase PAC1 which is involved in the dephosphorylation of MAP kinases was also looked at. There were significant differences in the response to different dose regimens for all the factors studied. Fractionated irradiation elicited an adaptive response with a sustained activation over 7 days of prosurvival p44 MAP kinase which was balanced by the increased activation of proapoptotic p54 SAP kinase up to 1 day post-irradiation, whereas, phosphorylated p38 MAP kinase showed a decrease at most time points. PAC1 was induced following fractionated irradiation and may be acting as a feed back regulator of p44 MAP kinase. The activation of SAP kinase after fractionated irradiation may be a stress response, whereas, constitutively activated p44 MAP kinase may play an important role in the induction of radioresistance during fractionated radiotherapy of cancer and may serve as a promising target for specific inhibitors to enhance the efficacy of radiotherapy.
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PMID:Fractionated and acute irradiation induced signaling in a murine tumor. 1722 87

Circadian rhythms are endogenous cycles with periods close to, but not exactly equal to, 24 h. In mammals, circadian rhythms are generated in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as several peripheral cell types, such as fibroblasts. Protein kinases are key regulators of the circadian molecular machinery. We investigated the role of the c-Jun N-terminal kinases (JNK), which belong to the mitogen-activated protein kinases family, in the regulation of circadian rhythms. In rat-1 fibroblasts, the p46 kDa, but not the p54 kDa, isoforms of JNK expressed circadian rhythms in phosphorylation. The JNK-inhibitor SP600125 dose-dependently extended the period of Period1-luciferase rhythms in rat-1 fibroblasts from 24.23+/-0.17-31.48+/-0.07 h. This treatment also dose-dependently delayed the onset of the bioluminescence rhythms. The effects of SP600125 on explant cultures from Period1-luciferase transgenic mice and Period2(Luciferase) knockin mice appeared tissue-specific. SP600125 lengthened the period in SCN, pineal gland, and lung explants in Period1-luciferase and Period2(Luciferase) mice. However, in the kidneys circadian rhythms were abolished in Period1-luciferase, while circadian rhythms were not affected by SP600125 treatment in Period2(Luciferase) mice. Valproic acid, already known to affect period length, enhanced JNK phosphorylation and, as predicted, shortened the period of the Period1-bioluminescence rhythms in rat-1 fibroblasts. In conclusion, our results showed that SP600125 treatment, as well as valproic acid, alters JNK phosphorylation levels, and modulates the period length in various tissues. We conclude that JNK phosphorylation levels may help to set the period length of mammalian circadian rhythms.
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PMID:c-Jun N-terminal kinase inhibitor SP600125 modulates the period of mammalian circadian rhythms. 1727 Mar 52

The CD150 receptor is expressed on thymocytes, activated and memory T cells, B cells, platelets, natural killer T cells, and mature dendritic cells, and is also detected on tumor cells of Hodgkin's lymphoma (HL) and diffuse large B-cell lymphoma with an activated B cell phenotype. Here, we report that the level of CD150 expression is elevated during B cell differentiation toward plasma cells. In primary tonsillar B cells and HL cell lines, CD150 signaling regulates the phosphorylation of three types of mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and Jun N-terminal kinase 1/2 (JNK1/2). CD150 induced ERK1/2 activation in primary tonsillar B cells and in two HL cell lines. CD150 mediated activation of JNK1/2 p54 and JNK2-gamma kinase isoforms in all CD150(+) B cell lines we tested. CD150 associated with the serine/threonine kinase hematopoetic progenitor kinase 1 (HPK1) regardless of CD150 tyrosine phosphorylation or binding of the SH2D1A adaptor protein to CD150, and HPK1 overexpression enhanced CD150-mediated JNK1/2 phosphorylation. CD150 ligation inhibited cell proliferation of all studied HL cell lines and induced apoptosis in L1236 HL cells that did not depend on JNK activity. As signaling through CD150 modulates MAPK activity in HL tumor cells, CD150 may contribute to regulation of tumor cell maintenance in low-rate proliferating HLs.
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PMID:CD150 regulates JNK1/2 activation in normal and Hodgkin's lymphoma B cells. 2023 52


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