Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors.
Activation of certain classes of G protein-coupled receptors (GPCRs) can lead to alterations in the actin cytoskeleton, gene transcription, cell transformation, and other processes that are known to be regulated by Rho family small-molecular-weight GTPases. Although these responses can occur indirectly via cross-talk from canonical heterotrimeric G protein cascades, it has recently been demonstrated that Dbl family Rho guanine nucleotide exchange factors (RhoGEFs) can serve as the direct downstream effectors of heterotrimeric G proteins. Heterotrimeric Galpha(12/13), Galpha(q), and Gbetagamma subunits are each now known to directly bind and regulate RhoGEFs. Atomic structures have recently been determined for several of these RhoGEFs and their G protein complexes, providing fresh insight into the molecular mechanisms of signal transduction between GPCRs and small molecular weight G proteins. This review covers what is currently known about the structure, function, and regulation of these recently recognized effectors of heterotrimeric G proteins.
Aittaleb
Mohamed
M
University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
Boguth
Cassandra A
CA
Tesmer
John J G
JJ
D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000502:physiology
D020662:Guanine Nucleotide Exchange Factors; D043562:Receptors, G-Protein-Coupled; D064067:Rho Guanine Nucleotide Exchange Factors; D020962:Heterotrimeric GTP-Binding Proteins