Identification of PKC activation as a novel mechanism for RGS2 protein up- regulation through phenotypic screening of natural product extracts
نویسندگان
چکیده
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA (A.R., P.J.S., D.H.S.); Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, USA (L.A., R.R.N., B.S.); Department of Pharmacology (C.C.), Department of Medicinal Chemistry (D.H.S.), Department of Microbiology and Immunology (D.H.S.), Department of Chemistry (D.H.S.), Center for Chemical Genomics, University of Michigan, Ann Arbor, MI, USA (D.H.S.); Unidad Estrategica de Bioprospección, Instituto Nacional de Biodiversidad (INBio), Santo Domingo de Heredia, Costa Rica & CIPRONA, Escuela de Química, Universidad de Costa Rica, 2060 San Pedro, Costa Rica (G.T-C.); Harvard Medical School, Boston, MA, USA (S.C., J.C.); University of Hawaii Cancer Center, Honolulu, HI, USA (S.C.) This article has not been copyedited and formatted. The final version may differ from this version. Molecular Pharmacology Fast Forward. Published on August 1, 2014 as DOI: 10.1124/mol.114.092403
منابع مشابه
Identification of protein kinase C activation as a novel mechanism for RGS2 protein upregulation through phenotypic screening of natural product extracts.
Biochemical high-throughput screening is widely used in drug discovery, using a variety of small molecule libraries. However, broader screening strategies may be more beneficial to identify novel biologic mechanisms. In the current study we used a β-galactosidase complementation method to screen a selection of microbial-derived pre-fractionated natural product extracts for those that increase r...
متن کاملSpecific regulation of RGS2 messenger RNA by angiotensin II in cultured vascular smooth muscle cells.
The effects of angiotensin II (Ang II) are mediated primarily by Ang II type 1 receptors, which in turn are coupled to heterotrimeric G proteins. After receptor activation, the G(alpha) and G(betagamma) subunits dissociate, contributing to the signaling cascades involving protein kinase C (PKC) activation. Regulators of G protein signaling (RGS proteins) comprise a class of proteins that have b...
متن کاملThe Implication of Androgens in the Presence of Protein Kinase C to Repair Alzheimer’s Disease-Induced Cognitive Dysfunction
Aging, as a major risk factor of memory deficiency, affects neural signaling pathways in hippocampus. In particular, age-dependent androgens deficiency causes cognitive impairments. Several enzymes like protein kinase C (PKC) are involved in memory deficiency. Indeed, PKC regulatory process mediates α-secretase activation to cleave APP in β-amyloid cascade and tau proteins phosphorylation mecha...
متن کاملIdentification of a cAMP-response Element in the RGS2 Promoter as a Key cis-Regulatory Element for RGS2 Transcriptional Regulation by Angiotensin II in Cultured VSMC
Background: Angiotensin II-induced RGS2 expression is an important negative feedback loop in blood pressure homeostasis. Result: A conserved CREB binding site is found in the RGS2 promoter and is associated with three SNPs identified in hypertensive patients. Conclusion: CREB links the angiotensin II/PKC/iPLA2β/PKA signaling and RGS2 transcription. Significance: This study delineates a negative...
متن کاملVirtual target screening to rapidly identify potential protein targets of natural products in drug discovery
Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must ...
متن کامل