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PMID: 19226283 Published · ppublish English Journal Article Review

Regulation of RhoGEF proteins by G12/13-coupled receptors.

British journal of pharmacology ·Vol. 158 ·No. 1 ·2009-09-00 ·Pages 41-9

Siehler S

Abstract

G protein-coupled receptors (GPCRs) represent a large family of seven transmembrane receptors, which communicate extracellular signals into the cellular lumen. The human genome contains 720-800 GPCRs, and their diverse signal characteristics are determined by their specific tissue and subcellular expression profiles, as well as their coupling profile to the various G protein families (G(s), G(i), G(q), G(12)). The G protein coupling pattern links GPCR activation to the specific downstream effector pathways. G(12/13) signalling of GPCRs has been studied only recently in more detail, and involves activation of RhoGTPase nucleotide exchange factors (RhoGEFs). Four mammalian RhoGEFs regulated by G(12/13) proteins are known: p115-RhoGEF, PSD-95/Disc-large/ZO-1 homology-RhoGEF, leukemia-associated RhoGEF and lymphoid blast crisis-RhoGEF. These link GPCRs to activation of the small monomeric GTPase RhoA, and other downstream effectors. Misregulated G(12/13) signalling is involved in multiple pathophysiological conditions such as cancer, cardiovascular diseases, arterial and pulmonary hypertension, and bronchial asthma. Specific targeting of G(12/13) signalling-related diseases of GPCRs hence provides novel therapeutic approaches. Assays to quantitatively measure GPCR-mediated activation of G(12/13) are only emerging, and are required to understand the G(12/13)-linked pharmacology. The review gives an overview of G(12/13) signalling of GPCRs with a focus on RhoGEF proteins as the immediate mediators of G(12/13) activation.

MeSH Terms
Animals GTP-Binding Protein alpha Subunits, G12-G13/chemistry,physiology Guanine Nucleotide Exchange Factors/chemistry,metabolism Humans Receptors, G-Protein-Coupled/chemistry,physiology Rho Guanine Nucleotide Exchange Factors Signal Transduction/physiology
Chemicals
ARHGEF1 protein, human Guanine Nucleotide Exchange Factors Receptors, G-Protein-Coupled Rho Guanine Nucleotide Exchange Factors GTP-Binding Protein alpha Subunits, G12-G13
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Siehler Sandra
Novartis Institutes for BioMedical Research Basel, Center for Proteomic Chemistry, Novartis Pharma AG, Basel, Switzerland. [email protected]
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
1476-5381
DOI
10.1111/j.1476-5381.2009.00121.x
Email
[email protected]
Published
2009-09-00
Epub
2009-00-18
Pages
41-9
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2795247
Subset
IM
External Links
PubMed source DOI: 10.1111/j.1476-5381.2009.00121.x PMC Full Text View journal details
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