Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor

Functional interaction and relevance to cell signaling

C. Hawkes, A. Amritraj, Richard G MacDonald, J. H. Jhamandas, S. Kar

Research output: Contribution to journalReview article

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)329-345
Number of pages17
JournalMolecular Neurobiology
Volume35
Issue number3
DOIs
StatePublished - Jan 1 2007

Fingerprint

IGF Type 2 Receptor
Heterotrimeric GTP-Binding Proteins
Insulin-Like Growth Factor II
GTP-Binding Proteins
G-Protein-Coupled Receptors
Cell Surface Receptors
Glycoproteins
Ligands
Enzymes

Keywords

  • G protein-coupled receptor
  • Heterotrimeric G protein
  • IGF-II/MGP

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor : Functional interaction and relevance to cell signaling. / Hawkes, C.; Amritraj, A.; MacDonald, Richard G; Jhamandas, J. H.; Kar, S.

In: Molecular Neurobiology, Vol. 35, No. 3, 01.01.2007, p. 329-345.

Research output: Contribution to journalReview article

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