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Article

Single Transmembrane Spanning Heterotrimeric G Protein-Coupled Receptors and Their Signaling Cascades

Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois

Abstract

I. Introduction

II. Activation and Inactivation of Heterotrimeric GTP-Binding Proteins

III. Receptor Protein Tyrosine Kinases

A. Epidermal Growth Factor Receptor

B. Insulin and Insulin-Like Growth Factor Receptors

C. Platelet-Derived Growth Factor and Fibroblast Growth Factor Receptors

IV. Other Single Transmembrane Receptors and Proteins Coupled to Heterotrimeric G Proteins

A. Amyloid Precursor Protein

B. C-Type Natriuretic Peptide Receptor

C. Zona Pellucida Glycoprotein Receptor

D. Integrins and Associated Proteins

E. T Cell Receptors

V. Concluding Remarks

Heptahelical of serpentine receptors such as the adrenergic receptors are well known to mediate their actions via heterotrimeric GTP-binding proteins. Likewise, receptors that traverse the cell membrane once have been shown to mediate their biological actions by activating several different mechanisms including stimulation of their intrinsic tyrosine kinase activities or the kinase activities of other proteins. Some of these single transmembrane receptors have an intrinsic guanylyl cyclase activity and can stimulate the cyclic GMP second messenger system; however, over the last few years, several studies have shown the involvement of heterotrimeric GTP-binding proteins in mediating signals that eventually culminate in the biological actions of single transmembrane spanning receptors and proteins. These receptors include the receptor tyrosine kinases that mediate the actions of growth factors such as epidermal growth factor, insulin, insulin-like growth factor as well as receptors for atrial natiuretic hormone or the zona pellucida protein (ZP3) and integrins. In this review, the significance of the coupling of the single transmembrane spanning receptors to G proteins has been highlighted by providing several examples of the concept that signaling via these receptors may involve the activation of multiple signaling cascades.

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