G-protein regulatory pathways: Rocketing into the twenty-first century

Abstract

Complex cellular responses involve the integration of heterotrimeric G protein systems with protein kinase signal transduction pathways. Key in this integration is the control of small GTP-binding proteins including Ras and Rho family members. In this paper, we discuss the control of signal transduction pathways by G proteins and their integration with specific tyrosine kinases. The integration of G proteins, kinases, and small GTP-binding proteins in controlling cellular responses is illustrated through the newly defined Gα -regulated pathways. Furthermore, the polymorphonuclear leukocyte provides a primary cell system for analyzing the integration of G proteins, kinases, and small GTP-binding proteins in controlling cellular functions such as superoxide production, adherence, chemotaxis, and granule secretion. J. Cell. Biochem. Suppls. 30/31:137-146, 1998. © 1998 Wiley-Liss, Inc.

Evaluation of the effects of peptide antibiotics human β‐defensins‐1/‐2 and LL‐37 on histamine release and prostaglandin D2production from mast cells

“…Among isoenzymes of PLC identified, only g subtype PLC is activated by G proteins, typically G q § . In addition, g + subunits of G proteins dissociated from G i/o § also regulate PLC g activity [31,32]. Since PTx is known to inhibit G i/o § but not G q § [33], our findings suggest that G i § and/or G o § type G proteins are involved in hBD-2-and LL-37-induced activation of PLC in mast cells.…”

Antimicrobial Peptides Human β-Defensins Stimulate Epidermal Keratinocyte Migration, Proliferation and Production of Proinflammatory Cytokines and Chemokines

“…The cytokine and chemokine producing activities of hBDs involved the G protein-and PLC-dependent pathway, as demonstrated by the inhibitory effects of PTx and U-73122 against hBDs, and confirmed by the reduction of cytokine and chemokine production following PLCb knockdown. Because PTx inhibits G i/o a proteins (Clapham, 1995), and as bg subunits of G proteins dissociated from G i/o a regulate PLCb activities (Kehrl, 1998;Knall and Johnson, 1998), it is possible that G i/o a coupled to PLCb participate in hBDmediated activation of keratinocytes. Although antimicrobial peptides including hBDs and LL-37 have been shown to function via G protein-coupled receptors, their specific receptors are not yet well known.…”

G Proteins in Drug Screening: From Analysis of Receptor-G Protein Specificity to Manipulation of GPCR-Mediated Signalling Pathways

“…Interaction of an activated receptor with a G protein promotes the exchange of guanosine diphosphate (GDP), bound to the α subunit, for guanosine triphosphate (GTP) and the subsequent dissociation of the Gα-GTP complex from the βγ heterodimer [1] or, alternatively, their molecular rearrangement [2,3]. Irrespective of whether G proteins operate by subunit dissociation or rearrangement, respectively, upon activation both Gα-GTP and βγ dimers interact with a variety of effector proteins including adenylyl cyclases (AC), phospholipases (PL), phosphodiesterases (PDE), and ion channels [4][5][6][7]. Signal termination is ensured by the hydrolysis of GTP, thereby returning the Gα protein to its basal GDP-bound state which is able to reassociate with βγ dimers to reform the αβγ heterotrimer [1,8].…”

“…Gα subunits all demonstrate the following common features: (i) GDP/GTP binding, (ii) GTPase activity, and (iii) Gβγ association. Nonetheless, Gα subunits can be distinguished by their specific interaction with effector proteins such as adenylyl cyclases and phospholipases [4,5,7], regulatory proteins of the RGS-and AGS family [46,47], G protein coupled receptor kinases (GRKs) [48], and their different profiles of receptor interaction.…”