Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Minibrain-related kinase (Mirk)/Dyrk1B is an arginine-directed serine/threonine kinase that is active in skeletal muscle development but is also expressed in various carcinomas. In the current study, the Met adaptor protein Ran-binding protein M (RanBPM) was identified as a Mirk-binding protein by yeast two-hybrid analysis. The Mirk-RanBPM association was confirmed by glutathione S-transferase pull-down assays, co-immunoprecipitation studies, and in vivo cross-linking. Met plays an important role in tumor cell invasion and cell migration. RanBPM has been reported to bind to the tyrosine kinase domain of the hepatocyte growth factor (HGF) receptor Met, enhance Met downstream signaling, and enhance HGF-induced A704 kidney carcinoma cell invasion (Wang, D., Li, Z., Messing, E. M., and Wu, G. (2002) J. Biol. Chem. 277, 36216-36222). We made a stable Mirk-inducible subline from nontransformed Mv1Lu lung epithelial cells and now demonstrate that induction of Mirk inhibited the migration of these cells in wounding experiments and inhibited their invasion through polycarbonate Transwell filters. Furthermore the ability of Mirk to inhibit Mv1Lu cell migration was attenuated when cells were exposed to HGF or to elevated levels of transiently expressed RanBPM. RanBPM inhibited the kinase activity of Mirk/Dyrk1B and Dyrk1A. In addition, RanBPM and HGF inhibited the function of Mirk as a transcriptional coactivator. Our findings suggest that Mirk plays a role in modulating cell migration through opposing the action of the Met signaling cascade adaptor protein RanBPM.
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PMID:Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M. 1450 Jul 17

Upon a certain DNA damage including cisplatin treatment, p73 is stabilized and exerts its growth-suppressive and/or proapoptotic function. However, the precise molecular basis by which the intracellular levels of p73 are regulated remains unclear. In the present study, we have identified RanBPM as a novel binding partner of p73alpha by yeast-based two-hybrid screening, and also found that RanBPM has an ability to stabilize p73alpha. GST pull-down assays and co-immunoprecipitation experiments revealed that RanBPM directly bound to the extreme COOH-terminal region of p73alpha, whereas it failed to interact with p53. Co-expression of RanBPM with p73alpha resulted in the nuclear translocation of RanBPM, and both proteins co-localized in cell nucleus as examined by indirect immunofluorescent staining. It is worth noting that the expression of RanBPM inhibited the ubiquitination of p73alpha, and thereby prolonged its half-life. Subsequent studies demonstrated that the proapoptotic activity of p73alpha was significantly enhanced in the presence of RanBPM. Taken together, our present findings implicate a novel role for RanBPM in the regulation of p73 stability and function.
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PMID:Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells. 1555 19

A yeast two-hybrid screen using the last 28 amino acids of the cytoplasmic domain of the neural cell adhesion molecule L1 identified RanBPM as an L1-interacting protein. RanBPM associates with L1 in vivo and the N-terminal region of RanBPM (N-RanBPM), containing the SPRY domain, is sufficient for the interaction with L1 in a glutathione S-transferase pull-down assay. L1 antibody patching dramatically changes the subcellular localization of N-RanBPM in transfected COS cells. Overexpression of N-RanBPM in COS cells reduces L1-triggered extracellular signal-regulated kinase 1/2 activation by 50% and overexpression of N-RanBPM in primary neurons inhibits L1-mediated neurite outgrowth and branching. These data suggest that RanBPM is an adaptor protein that links L1 to the extracellular signal-regulated kinase/MAPK pathway.
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PMID:RanBPM is an L1-interacting protein that regulates L1-mediated mitogen-activated protein kinase activation. 1600 Jan 62

Human Dectin-1, a type II transmembrane receptor, is alternatively spliced, generating eight isoforms. Of these isoforms, the isoform E (hDectin-1E) is structurally unique, containing a complete C-type lectin-like domain as well as an ITAM-like sequence. So far, little is known about its function. In the present study, we demonstrated that hDectin-1E was not secreted and it mainly resided in the cytoplasm. Using yeast two-hybrid screening, we identified a Ran-binding protein, RanBPM, as an interacting partner of hDectin-1E. GST pull-down assays showed that RanBPM interacted directly with hDectin-1E and the region containing SPRY domain was sufficient for the interaction. The binding of hDectin-1E and RanBPM was further confirmed in vivo by co-immunoprecipitation assay and confocal microscopic analysis. Taken together, our data provide a clue to the understanding of the function about hDectin-1E.
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PMID:Human Dectin-1 isoform E is a cytoplasmic protein and interacts with RanBPM. 1687 Jan 51

RanBPM as a novel binding protein can interact with neurotrophin receptor p75NTR and tyrosine kinase receptor Met which has a similar tyrosine kinase structure as receptor TrkA has. Whether RanBPM interacts with neurotrophin receptor TrkA has not been established to date. In this study, using yeast two-hybrid system, it was identified that RanBPM bound to the intracellular domain (ICD) of neurotrophin receptor TrkA through its SPRY motif. We confirmed the formation of complexes between RanBPM and TrkA by co-immunoprecipitation studies and GST pull-down assays. The region of TrkA interacted with the SPRY domain of RanBPM was located in its tyrosine kinase domain. Furthermore, coimmunoprecipitaiton revealed endogenous RanBPM and receptors TrkA did interact in several mammalian cell lines. It was found that the overexpression of RanBPM could inhibit NGF-induced increase of nuclear factor of activated T cells (NFAT) dependent luciferase expression through its interaction with receptor TrkA, and NFAT transcriptional activity plays an important role in neuronal signal transduction. These data suggested that RanBPM could participate in neurotrophin-mediated gene transcription and expression by its binding to TrkA.
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PMID:The Ran binding protein RanBPM interacts with TrkA receptor. 1695 15

The evolutionarily conserved lethal giant larvae (Lgl) tumor suppressor gene has an essential role in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. However, the precise molecular mechanism by which the Lgl carries out its function remains obscure. In the current study, we have identified Ran-binding protein M (RanBPM) as a novel binding partner of Mgl-1, a mammalian homolog of Drosophila tumor suppressor protein lethal (2) giant larvae (L(2)gl) by yeast two-hybrid screening. RanBPM seems to act as a scaffolding protein with a modulatory function with respect to Mgl-1. The Mgl-1 and RanBPM association was confirmed by co-immunoprecipitation and GST pull-down experiments. Additionally, expression of RanBPM resulted in inhibition of Mgl-1 degradation, and thereby extended the half-life of Mgl-1. Furthermore, the ability of Mgl-1 activity in cell migration and colony formation assay was enhanced by RanBPM. Taken together, our findings reveal that RanBPM plays a novel role in regulating Mgl-1 stability and contributes to its biological function as a tumor suppressor.
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PMID:Stability and function of mammalian lethal giant larvae-1 oncoprotein are regulated by the scaffolding protein RanBPM. 2082 63

BLT2, a low affinity receptor for leukotriene B4 (LTB4), is a member of the G protein-coupled receptor family and is involved in many signal transduction pathways associated with various cellular phenotypes, including chemotactic motility. However, the regulatory mechanism for BLT2 has not yet been demonstrated. To understand the regulatory mechanism of BLT2, we screened and identified the proteins that bind to BLT2. Using a yeast two-hybrid assay with the BLT2 C-terminal domain as bait, we found that RanBPM, a previously proposed scaffold protein, interacts with BLT2. We demonstrated the specific interaction between BLT2 and RanBPM by GST pulldown assay and co-immunoprecipitation assay. To elucidate the biological function of the RanBPM-BLT2 interaction, we evaluated the effects of RanBPM overexpression or knockdown. We found that BLT2-mediated motility was severely attenuated by RanBPM overexpression and that knockdown of endogenous RanBPM by shRNA strongly promoted BLT2-mediated motility, suggesting a negative regulatory function of RanBPM toward BLT2. Furthermore, we observed that the addition of BLT2 ligands caused the dissociation of BLT2 and RanBPM, thus releasing the negative regulatory effect of RanBPM. Finally, we propose that Akt-induced BLT2 phosphorylation at residue Thr(355), which occurs after the addition of BLT2 ligands, is a potential mechanism by which BLT2 dissociates from RanBPM, resulting in stimulation of BLT2 signaling. Taken together, our results suggest that RanBPM acts as a negative regulator of BLT2 signaling to attenuate BLT2-mediated cell motility.
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PMID:RanBPM protein acts as a negative regulator of BLT2 receptor to attenuate BLT2-mediated cell motility. 2392 9