The human orthologue of CdGAP is a phosphoprotein and a GTPase-activating protein for Cdc42 and Rac1 but not RhoA

Biology of the Cell
Joseph TcherkezianN Lamarche-Vane

Abstract

Rho GTPases regulate a wide range of cellular functions affecting both cell proliferation and cytoskeletal dynamics. They cycle between inactive GDP- and active GTP-bound states. This cycle is tightly regulated by GEFs (guanine nucleotide-exchange factors) and GAPs (GTPase-activating proteins). Mouse CdGAP (mCdc42 GTPase-activating protein) has been previously identified and characterized as a specific GAP for Rac1 and Cdc42, but not for RhoA. It consists of an N-terminal RhoGAP domain and a C-terminal proline-rich region. In addition, CdGAP-related genes are present in both vertebrates and invertebrates. We have recently reported that two predominant isoforms of CdGAP (250 and 90 kDa) exist in specific mouse tissues. In the present study, we have identified and characterized human CdGAP (KIAA1204) which shares 76% sequence identity to the long isoform of mCdGAP (mCdGAP-l). Similar to mCdGAP, it is active in vitro and in vivo on both Cdc42 and Rac1, but not RhoA, and is phosphorylated in vivo on serine and threonine residues. In contrast with mCdGAP-l, human CdGAP interacts with ERK1/2 (extracellular-signal-regulated kinase 1/2) through a region that does not involve a DEF (docking site for ERK Phe-Xaa-Phe-Pro) domain. Also, th...Continue Reading

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Citations

Dec 30, 2015·Biochemical and Biophysical Research Communications·Satoshi EnomotoTakao Hamakubo
May 11, 2012·Trends in Cell Biology·Ming LiuYi Zheng
Jan 16, 2007·Biology of the Cell·Joseph Tcherkezian, Nathalie Lamarche-Vane
Jan 16, 2013·International Journal of Cancer. Journal International Du Cancer·Benedek BozókyGeorge Klein
May 14, 2011·American Journal of Human Genetics·Laura SouthgateRichard C Trembath
Mar 17, 2018·Oncotarget·Ali Ben Djoudi OuaddaNathalie Lamarche-Vane
Dec 8, 2020·American Journal of Medical Genetics. Part a·Franziska SchnabelMartin Zenker
Dec 13, 2006·The Journal of Biological Chemistry·Eric Ian DanekNathalie Lamarche-Vane
Jun 11, 2021·Molecular Biology Reports·Natalia Ruiz-LafuenteAntonio Parrado

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