Document Detail


Identification of novel signaling roles and targets for Gα and Gβγ downstream of the IGF-1R in vascular smooth muscle cells.
MedLine Citation:
PMID:  23186281     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Vascular dysfunction is the underlying cause of nearly 80% of heart disease cases, and its initiation and progression can be exacerbated by circulating factors, such as insulin-like growth factor-1 (IGF-1). IGF-1, which is highly homologous to insulin, elicits a response via a classical tyrosine kinase receptor, the IGF-1R. However, it has been suggested that the IGF-1R may also be coupled to a heterotrimeric G protein and can thus modulate cellular processes via this alternate pathway. The objective of this study was to investigate the structural aspects of IGR-1R coupling to a heterotrimeric G protein in vascular smooth muscle cells (VSMCs), as well as study the contribution of this pathway to cellular responses that are related to vascular disease. We found that the intracellular subunit of the IGF-1R precipitates with two G protein subunits. The Gβγ-mediated pathway contributes to both proliferation and migration. We also show that IGF-1 specifically activates Gαi and can directly interact with both Gαi1 and Gαi2. A phospho-screen using a novel, specific Gαi peptide inhibitor reveals a number of potential downstream effectors of this pathway, although our results show that it is not essential for SMC proliferation or migration.
Authors:
Raissa Perrault; Peter Zahradka
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-28
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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