Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate regulation of D2 receptor (D2R) gene expression by protein kinases, we evaluated effects of constitutively active MAPK kinase kinase (MEKK), Ca2+/calmodulin-dependent protein kinase (CaMK) II, CaMKIV and cyclic AMP-dependent protein kinase (PKA) on D2R promoter activity using luciferase reporter gene assays. A 1.5-kbp fragment containing the rat D2R promoter was cloned upstream of the reporter and transfected into D2R-expressing NB2A cells or nonexpressing NG108-15 and C6 glioma cells. MEKK and CaMKII, but not CaMKIV and PKA, increased promoter activity 4.5- and 1.5-fold, respectively, in NB2A cells. Inhibitory effects of a MEK inhibitor and lack of effect by dominant negative (DN)-JNK1 or DN-p38MAPK revealed that ERK but not JNK and p38MAPK is involved in MEKK-induced promoter activation. Deletion and mutation of the promoter revealed that the MEKK-responsive region was Sp1 site B between nucleotides -56 and -47. Overexpression of Sp1 suppressed promoter activity without affecting MEKK-induced activation. Interestingly, overexpression of Zif268 increased promoter activity through the region between nucleotides -56 and -36. Increased activity by Zif268 was additive with CaMKII-induced activation but not with activation induced by MEKK. Co-transfection with CaMKII stimulated nuclear translocation of Zif268. These results suggest that ERK and CaMKII positively regulate the D2R promoter and that Zif268 is a potential transcription factor for the CaMKII-dependent pathway.
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PMID:Activation of the rat dopamine D2 receptor promoter by mitogen-activated protein kinase and Ca2+/calmodulin-dependent protein kinase II pathways. 1242 50

Recent studies suggest that CaM kinase II is involved in light-induced phase delays and induction of Per1 and Per2 genes in the hamster suprachiasmatic nucleus (SCN) (Yokota et al.,2001). We focused on intracellular mechanisms of the CaM kinase II-induced mPer1 gene expression. Immunoblotting and immunohistochemical analyses with isoform-specific antibodies against different isoforms of CaM kinase II and CaM kinase IV showed abundant expression of the delta isoform of CaM kinase II without significant expression of CaM kinase IV in the lateral ventral region of the rat SCN. We next defined the CaM kinase II-responsive region on the mPer1 promoter using a luciferase reporter gene assay. Transfection of the constitutively-active CaM kinase IIdelta greatly increased mPer1 promoter activity in NG108-15 cells and increased activity slightly but significantly in NB2A and C6 glioma cells. Similarly, transfection of a constitutively-active MEKK, an upstream kinase of mitogen-activated protein kinase (MAPK), greatly increased promoter activity in NB2A cells. Deletion and mutation analyses of the mPer1 promoter revealed that a 5'-GAGGGG-3' sequence motif near exon 1B, in which several zinc finger proteins seem to bind, was essential for the CaM kinase II-induced activation of the mPer1 promoter. These results suggest that CaM kinase IIdelta but not CaM kinase IV plays an essential role for mPer1 expression through the 5'-GAGGGG-3' motif on the mPer1 promoter.
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PMID:Involvement of calcium/calmodulin-dependent protein kinase II in the induction of mPer1. 1269 5

In the present study, we investigated the effect of simultaneous downregulation of uPAR and cathepsin B (pUC), alone or in combination with radiation, on JNK-MAPK signaling pathway in regulating the migration of non-GICs (glioma-initiating cells) and GICs. The increase in the expression of p-JNK with pUC treatment was mostly localized to nucleus whereas increase in the expression of p-JNK with radiation and overexpression of uPAR and cathepsin B was confined to cytoplasm of the cells. Depletion of cytosolic p-JNK with pUC treatment inhibited migration by downregulating the expression of the adapter proteins of the focal adhesion complex. We also observed that knockdown of uPAR and cathepsin B regulated the Ras-Pak-1 pathway to induce the translocation of p-JNK from cytosol to nucleus. In control cells, Pak-1 served as a functional inhibitor for MEKK-1, which inhibits the complex formation of MEKK-1 and p-JNK and thus inhibits the translocation of this complex into nucleus. Hence, we conclude that glioma cells utilize the availability of cytosolic p-JNK in driving the cells towards migration. Finally, treating the cells with pUC alone or in combination with radiation induced the translocation of the MEKK-1-p-JNK complex from cytosol to nucleus, thereby inhibiting the migration of glioma cells.
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PMID:uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells. 2469 10