ERK1/2, phosphorylation

ERK1/2 phosphorylation by involving G /o proteins, PKC and tyrosine kinase-dependent and -independent pathways. It has been found that Cl-IB-MECA produced a biphasic effect on cAMP accumulation with a stimulatory action starting at a concentration of 3 nM. This activity was triggered through PLC/PKC and not via direct Gs coupling (Germack and Dickenson 2004, 2005). 

VEGF-ERK1/2 phosphorylation in human HUVEC cells 60... 

G-protein signaling 2 (RGS2) in hypertensive patients increases calcium mobilization and ERK1/2 phosphorylation induced by angiotensin II. J Hypertens 24 1115-1124... 

FIGURE 13.S ERK1/2 phosphorylation affects Cf-PS-induced cell proliferation. 

KohoutTA, Nicholas SL, Perry SJ, Reinhart G, Junger S, Struthers RS. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J Biol Chem 2004 279(22) 23214-23222. 

A recent observation shows that P-carotene was able to counteract the dangerous effect of 7-ketocholesterol in human macrophages by limiting the apoptotic processes reducing the intracellular ROS production and inhibiting the phosphorylation of p38, JNK, and ERK1/2 induced by the oxysterol (Palozza et al., 2007b). 

MAP kinase signaling modules typically comprise a cassette of three protein kinases (Fig. 7.2A). For example, ERK (two isoforms in mammalian cells, ERK1/2) is phosphorylated (at Thr and Tyr residues in the activation loop of its catalytic domain by an upstream MAP kinase kinase (in this case, MEK) which is, in turn, phosphorylated and activated by a MAP kinase kinase kinase, in this instance, a member of the Raf group) (Fig. 7.2A). 

Besides ERK1/2, there is experimental evidence that adenosine A3 receptors also activate p38 MAPKs in hCHO-A3 cells (Hammarberg et al. 2004). Furthermore, it has been demonstrated that A3 receptor stimulation is able to increase p38 phosphorylation in human hypoxic melanoma, glioblastoma and colon carcinoma cells (Merighi et al. 2005b, 2006, 2007a). 

Fig. 3.3 The ERK/MAP kinase signaling pathway cytokines and growth factors activate tyrosine kinase to which the adaptor protein Grb2 binds. This localizes SOS to plasma membrane. RAS is then activated by SOS. Activated RAS then binds to RAF, which forms a transient membraneanchoring signal. Active RAF kinase phosphorylates MEK. The activated MEK phosphorylates ERK1/ERK2, which also migrates to the nucleus to phosphorylate ELK-1, Etsl/2 and CREB, resulting in the activation and expression of respective genes (see Color Insert)...

Joy S, Siow RC, Rowlands DJ, Becker M, Wyatt AW, Aaronson PI, Coen CW, Kallo I, Jacob R, Mann GE. 2006. The isoflavone Equol mediates rapid vascular relaxation Ca2 + -independent activation of endothelial nitric-oxide synthase/Hsp90 involving ERK1/2 and Akt phosphorylation in human endothelial cells. J Biol Chem 281 27335-27345. 

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