Format

Send to

Choose Destination
Bioessays. 2016 Apr;38(4):379-93. doi: 10.1002/bies.201500133. Epub 2016 Feb 16.

Heterotrimeric G protein signaling via GIV/Girdin: Breaking the rules of engagement, space, and time.

Author information

1
Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
2
Department of Cell and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.

Abstract

Canonical signal transduction via heterotrimeric G proteins is spatially and temporally restricted, that is, triggered exclusively at the plasma membrane (PM), only by agonist activation of G protein-coupled receptors (GPCRs) via a process that completes within a few hundred milliseconds. Recently, a rapidly emerging paradigm has revealed a non-canonical pathway for activation of heterotrimeric G proteins by the non-receptor guanidine-nucleotide exchange factor (GEF), GIV/Girdin. This pathway has distinctive temporal and spatial features and an unusual profile of receptor engagement: diverse classes of receptors, not just GPCRs can engage with GIV to trigger such activation. Such activation is spatially and temporally unrestricted, that is, can occur both at the PM and on internal membranes discontinuous with the PM, and can continue for prolonged periods of time. Here, we provide the most complete up-to-date review of the molecular mechanisms that govern the unique spatiotemporal aspects of non-canonical G protein activation by GIV and the relevance of this new paradigm in health and disease.

KEYWORDS:

Golgi; autophagy; cdk5: Girdin; growth factor receptor tyrosine kinases; heterotrimeric G proteins

PMID:
26879989
PMCID:
PMC5123561
DOI:
10.1002/bies.201500133
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center