By P.Michael Conn
Oregon well-being Sciences Univ., Portland. built-in overview of membrane receptor-initiated mobile signalling and nuclear receptor-initiated gene law. supplies an in-depth therapy of cyclic AMP, protein kinases, and protein phosphatases. For scientific and base researchers.
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The M2-muscarinic and α2-adrenergic receptors) triggers the Ras–MAPK cascade through a complex mechanism that may involve stimulation of Src tyrosine kinase activity by their Gβγ dimer. , the epidermal growth factor or the platelet-derived growth factor receptors) and/or the Shc adapter molecule, which binds to a second adaptor, the Grb2 protein, through Src-homology 2 (SH2) domains; since Grb2 and the guanosine nucleotide exchange factor Sos1 are constitutively associated, the Gβγ-mediated recruitment of Grb2 to activated (tyrosine-phosphorylated) Shc augments the Shc-associated guanine nucleotide exchange factor activity leading to GDP➝GTP exchange and activation of Ras.
Totowa, NJ. 27 28 Part I / Signaling Mechanisms Initiated by Cell Surface Receptors Fig. 1. Conserved amino acid sequence motifs in large and small GTPases. The regions indicated as G1–G4 contain amino acids that contribute to GTP binding and hydrolysis and are present in the same relative order in Ras-like GTPases, EF-Tu, and heterotrimeric Gα-subunits. The consensus sequence in Gα-subunits are G1, KLLLGAGESGKSTIV; G2, DXLRXRVTT GIVE, G3, MFDVGGQR; and G4, ILFLNKKD. Ras-like GTP binding proteins are small, 20–25 kDa proteins, which share a common regulatory mechanism that cycles between an inactive GDP-bound state and an active GTP-bound state.
9. , α1B-adrenergic receptor (α1B AR) and muscarinic M1-acetylcholine receptor (M1AChR)] coupled to PTX-insensitive (Gαq) G proteins. Gαq activates phospholipase Cβ1 resulting in the conversion of phosphatidylinositol 4,5-biphosphate to inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), which in turn contributes to the activation of protein kinase C (PKC). PKC then activates Raf kinase by a still poorly understood mechanism. ) to activate the Ras-regulated MAP kinase cascade (see text for details).