| Structural highlights
Function
[ARHG7_HUMAN] Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions (By similarity). May function as a positive regulator of apoptosis. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess a approximately 200 residue catalytic Dbl-homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human PAK-interacting exchange protein (betaPIX). The domain is composed of 11 alpha-helices that form a flattened, elongated bundle. The structure explains a large body of mutagenesis data, which, along with sequence comparisons, identify the GTPase interaction site as a surface formed by three conserved helices near the center of one face of the domain. Proximity of the site to the DH C-terminus suggests a means by which PH-ligand interactions may be coupled to DH-GTPase interactions to regulate signaling through the Dbl proteins in vivo.
Structure and mutagenesis of the Dbl homology domain.,Aghazadeh B, Zhu K, Kubiseski TJ, Liu GA, Pawson T, Zheng Y, Rosen MK Nat Struct Biol. 1998 Dec;5(12):1098-107. PMID:9846881[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhan L, Rosenberg A, Bergami KC, Yu M, Xuan Z, Jaffe AB, Allred C, Muthuswamy SK. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell. 2008 Nov 28;135(5):865-78. doi: 10.1016/j.cell.2008.09.045. PMID:19041750 doi:10.1016/j.cell.2008.09.045
- ↑ Nola S, Sebbagh M, Marchetto S, Osmani N, Nourry C, Audebert S, Navarro C, Rachel R, Montcouquiol M, Sans N, Etienne-Manneville S, Borg JP, Santoni MJ. Scrib regulates PAK activity during the cell migration process. Hum Mol Genet. 2008 Nov 15;17(22):3552-65. doi: 10.1093/hmg/ddn248. Epub 2008 Aug, 20. PMID:18716323 doi:10.1093/hmg/ddn248
- ↑ Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR. Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron. 2008 Jan 10;57(1):94-107. doi: 10.1016/j.neuron.2007.11.016. PMID:18184567 doi:http://dx.doi.org/10.1016/j.neuron.2007.11.016
- ↑ Aghazadeh B, Zhu K, Kubiseski TJ, Liu GA, Pawson T, Zheng Y, Rosen MK. Structure and mutagenesis of the Dbl homology domain. Nat Struct Biol. 1998 Dec;5(12):1098-107. PMID:9846881 doi:http://dx.doi.org/10.1038/4209
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