Signaling pathways, Effects

The hormonal stimulation of adenylyl cyclase is effected by a transmembrane signaling pathway consisting of three components, all membrane-associated. Binding of hormone to the external surface of a hormone receptor causes a conformational change in this transmembrane protein, which in turn stimulates a GTP-binding protein (abbreviated G protein). G proteins are heterotrimeric proteins consisting of a- (45-47 kD), /3- (35 kD), and y- (7-9 kD) subunits. The a-subunit binds GDP or GTP and has an intrinsic, slow... 

Apelin receptors activate several signalling pathways including coupling through inhibitory G-proteins (G ) and Ras-independent activation of extracellular-regulated kinases (ERKs) via protein kinase C (PKC). The apelin receptor is one of number of G-protein-coupled receptors that can act as an alternative coreceptor for entry into cells of HIV and simian immunodeficiency vims (SIV) strains in human U87 cells expressing CD4 in vitro. Apelin peptides blocks entry of HIV but display different potencies, with apelin-36 being more effective than shorter sequences [3]. 

Components of the JAK-STAT signaling pathway represent novel targets for pharmacological interventions [4]. Recently, a specific and orally active JAK3 antagonist was identified from screening of a chemical library for inhibitors of in vitro JAK3 kinase activity. The most effective compound, CP-690,550, was shown... 

The concept of drug development is based on the findings that retinoid receptors (RARs and RXRs) offer a new approach by targeting different genes depending on the activated retinoid receptor complexes. The multiplicity of these retinoid signaling pathways affords potential for therapeutic opportunity as well as retinoid therapy associated undesired side effects. It is possible that the indiscriminate activation of all pathways by nonspecific retinoid ligands could lead to unacceptable side effects so that any enhanced efficacy would be obtained at the cost of enhanced toxicity. 

In chronic myelogenous leukemia (CML) as well as in a subset of acute lymphoblastic leukemia (ALL) Bcr-Abl, a fusion protein of c-Abl and the breakpoint cluster region (bcr), is expressed in the cytosol of leukemic cells. This fusion protein forms homo-oligomeric complexes that display elevated kinase activity and is the causative molecular abnormality in CML and certain ALL. The transforming effect of Bcr-Abl is mediated by numerous downstream signaling pathways, including protein kinase C (PKC), Ras-Raf-ERK MAPK, JAK-STAT (see below), and PI3-kinase pathways. 

Although toxic agents have the potential to cause necrosis, some of them can interfere with intracellular signaling pathways and induce apoptosis instead of necrosis. It seems that organotin(IV) compounds exert their toxic effects involving all these processes. The precise balance of these actions and their outcomes may differ radically from one cell type to another and among different organisms. 

While multiple signaling pathways are implicated in mediating the proliferative effects of CXCL12, only Akt activation, p38 activation, and suppression of cAMP levels have been shown to influence the survival response. Vlahakis et al. (2002) demonstrated that CXCL12 regulates survival in CD4-t T lymphocytes via the balance of pro-survival Akt activation and pro-apoptotic p38 activation. Whether the cellular response to CXCL12 was survival or apoptosis depended on coincident activation of these pathways by other factors. 

The Effect of CXCR4-Mediated Signaling Pathway on Neuronal Activity and Neurotransmitter Release... 

KIM H, PETERSON T G and BARNES s (1998) Mechanism of action of the soy isoflavone genistein emerging role for its effects via transforming growth factor 3 signalling pathways. J Clin Nutr. 68 (6 Suppl) 1418S-1425S. 

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