Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor:Functional interaction and relevance to cell signaling

Hawkes, C. and Amritraj, A. and MacDonald, R. G. and Jhamandas, J. H. and Kar, S. (2007) Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor:Functional interaction and relevance to cell signaling. Molecular Neurobiology, 35 (3). pp. 329-345. ISSN 0893-7648

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Abstract

The G protein-coupled receptor (GPCR) family represents the largest and most versatile group of cell surface receptors. Classical GPCR signaling constitutes ligand binding to a seven-transmembrane domain receptor, receptor interaction with a heterotrimeric G protein, and the subsequent activation or inhibition of downstream intracellular effectors to mediate a cellular response. However, recent reports on direct, receptor-independent G protein activation, G protein-independent signaling by GPCRs, and signaling of nonheptahelical receptors via trimeric G proteins have highlighted the intrinsic complexities of G protein signaling mechanisms. The insulin-like growth factor-II/mannose-6 phosphate (IGF-II/M6P) receptor is a single-transmembrane glycoprotein whose principal function is the intracellular transport of lysosomal enzymes. In addition, the receptor also mediates some biological effects in response to IGF-II binding in both neuronal and nonneuronal systems. Multidisciplinary efforts to elucidate the intracellular signaling pathways that underlie these effects have generated data to suggest that the IGF-II/M6P receptor might mediate transmembrane signaling via a G protein-coupled mechanism. The purpose of this review is to outline the characteristics of traditional and nontraditional GPCRs, to relate the IGF-II/M6P receptor's structure with its role in G protein-coupled signaling and to summarize evidence gathered over the years regarding the putative signaling of the IGF-II/M6P receptor mediated by a G protein.

Item Type:
Journal Article
Journal or Publication Title:
Molecular Neurobiology
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800/2804
Subjects:
ID Code:
137322
Deposited By:
Deposited On:
04 Oct 2019 15:15
Refereed?:
Yes
Published?:
Published
Last Modified:
26 May 2020 16:10