G protein in signal transduction

Simon M, Strathmann M, Gautam N. Diversity of G proteins in signal transduction. Science 1991 252 802-808. 

GM-CSF and IL-3 have been shown to compete for receptors in some types of cells (e.g. eosinophils and KG-1 cells), indicating some structural homology between GM-CSF and IL-3 receptors, perhaps because they share certain subunits or adapter proteins. GM-CSF occupancy results in phosphorylation of certain proteins, and because the receptor possesses no inherent kinase activity, receptor occupancy must be linked to kinase activity via the generation of second messenger molecules. Pretreatment of cells with pertussis toxin abolishes the effects of GM-CSF, indicating the involvement of G-proteins in signal transduction. Priming of neutrophil functions with GM-CSF involves the activation of phospholipases A2 and D. 

This GTP-GDP cycle of EF-Tu is reminiscent of those of the heterotrimeric G proteins in signal transduction (Section 15.1.2) and the Ras proteins in growth control (Section 15.4.2). This similarity is due to their evolutionary heritage, inasmuch as the amino-terminal domain of EF-Tu is homologous to the P-loop NTPase domains in the other G proteins. 

Bimbaumer, L. (1990). G-proteins in signal transduction. Annu. Rev. Pharmacol. Toxicol. 30, 675-705. 

Spiegel, A. M. (1996) Defects in G protein-coupled signal transduction in human disease. Anna. Rev. Physiol. 58, 143-70. 

An exciting development in G-protein-mediated signal transduction research has been the realization that proteins produced by oncogenes (cancer-causing genes) are also GTP-binding proteins. 

It is likely that phosducins play a role in many G-protein coupled signal transduction pathways. Phosducin-like proteins have been identified in a variety of tissues, e.g., in brain and in the pineal gland. 

Hashim, S., Y.Y. Liu, R. Wang, and M.B. Anand-Srivastava. 2002. Streptozotocin-induced diabetes impairs G-protein linked signal transduction in vascular smooth muscle. Mol. Cell. Biochem. 240 57-65. 

Figure 21.14. Regulatory Cascade for Glycogen Breakdown. Glycogen degradation is stimulated by hormone binding to 7TM receptors. Hormone binding initiates a G-protein-dependent signal-transduction pathway that results in the phosphorylation and activation of glycogen phosphorylase.

Platelets from SHR exhibit increased sensitivity to thrombin and PGE, than platelets from WKY rats. Both of these agonists produce their effects by a G protein mediated signal transduction mechanism leading to activation of PI-PLC and adenylyl cyclase respectively. Enhanced signal transduction at the G protein level may be responsible for a greater adenylyl cyclase, and possibly PI-PLC, activity in SHR than in WKY platelets. 

Fig. 3. The G-protein dependent signal transduction cycle. The signal transduction unit is represented by R (receptor), G (G protein), and E (effector). G is composed of Ga wifh bound GTP or GDP and of GPy. The acfive and inactive complexes or proteins are shown in black and grey, respectively. S represents the stimulus that triggers the cycle. Proteins interacting in a complex ore linked by hyphens...

Spiegel AM (1998) Introduction to G-protein-coupled signal transduction and human disease. In Spiegel AM (ed) G proteins, receptors, and disease. Humana, Totowa, NJ,... 

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