Regulation of RhoGEF proteins by G12/13-coupled receptors
| Autor: | Sandra Siehler |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Pharmacology
RHOA Effector G protein viruses GTP-Binding Protein alpha Subunits fungi Reviews GTPase Biology GTP-Binding Protein alpha Subunits G12-G13 Rhodopsin-like receptors Receptors G-Protein-Coupled Cell biology biology.protein Animals Guanine Nucleotide Exchange Factors Humans Receptor Rho Guanine Nucleotide Exchange Factors Signal Transduction G protein-coupled receptor |
| Zdroj: | British Journal of Pharmacology. 158:41-49 |
| ISSN: | 1476-5381 0007-1188 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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