Receptors and G proteins as primary components of transmembrane signal transduction

Abstract

Seven-transmembrane receptors signal through nucleotide-binding proteins (G proteins) into the cell. G proteins are membrane-associated proteins composed of three subunits termed alpha, beta and gamma, of which the G alpha subunit classifies the heterotrimer. So far, 23 different mammalian G alpha subunits are known, which are grouped in four subfamilies (Gs, Gi, Gq, G12) on the basis of their amino acid similarity. They carry an endogenous GTPase activity allowing reversible functional coupling between ligand-bound receptors and effectors such as enzymes and ion channels. In addition, five G beta and seven G gamma subunits have been identified which form tightly associated beta gamma heterodimers. Upon activation by a ligand-bound receptor the G protein dissociates into G alpha and G beta gamma, which both transmit signal by interacting with effectors. On the G protein level, specificity and selectivity of the incoming signal is accomplished by G protein trimers composed of distinct subunits. On the other hand, many receptors have been shown to activate different G proteins, thereby regulating diverse signal transduction pathways.

The CXC Chemokine Receptor 2, CXCR2, Is the Putative Receptor for ELR+ CXC Chemokine-Induced Angiogenic Activity

“…PTx, isolated from the bacteria Bordetella pertussis, is known to inhibit signal transduction mediated by certain G proteins, such as the G i /G o proteins, following ADP ribosylation of the G␣ subunit of the heterotrimeric G protein species (41,42). Signal transduction mediated by ligand binding of CXCR2 has been shown to be dependent on the interaction of the chemokine receptor with the PTx-sensitive G i2 G protein in neutrophils and 293 cells stably transfected to express CXCR2 (43,44).…”

“…Pellets were surgically implanted into corneal stromal micropockets created 1 mm medial to the lateral corneal limbus of C57BL/6 CXCR2 Ϫ/Ϫ and CXCR2 ϩ/ϩ mice (9 -10 wk old, derived from the strain developed at Genentech (South San Francisco, CA) by Cacalano et al (26), a gift from Dr. Robert Terkeltaub, and maintained by Ann Richmond). Five days postimplantation, corneas were photographed at an incipient angle of [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] o from the polar axis in the meridian containing the pellet, using a Zeiss split lamp. Images were digitalized and processed by subtractive color filters (Adobe Photoshop 4.0; Adobe Systems, Mountain View, CA): the fraction of the total corneal image that was vascularized (vascular area), and the ratio of pixels marking neovascular capillaries, both within the vascularized region (regional vascular density) and within the total corneal image (total vascular density), were calculated using the Bioquant software (Nashville, TN).…”

Potential roles of heterotrimeric G proteins of the endomembrane system

“…Furthermore, mastoparan abolishes the membrane potential of isolated secretory granules (G. Ahnert-Hilger and R. Jahn, unpublished). Other approaches exploring the role of G proteins involve specific antibodies and purified G proteins as well as overexpression of wild type and constitutively activated isoforms and introduction of antisense oligonucleotides into target cells [4,25,26].…”

Modulation of α2-Adrenoceptor Functions by Heterotrimeric Gαi Protein Isoforms

“…The G i subfamily of G␣ subunits comprises three highly related members, G␣ i1 , G␣ i2 , and G␣ i3 (Gerhardt and Neubig, 1991;Nü rnberg et al, 1995), which are characterized by their sensitivity to pertussis toxin. The three G␣ i subunits are encoded by distinct genes, termed Gnai1, Gnai2, and Gnai3 (Offermanns, 2003).…”