Reactome | RHOC GAPs stimulate RHOC GTPase activity

RHOC GAPs stimulate RHOC GTPase activity

Stable Identifier

R-HSA-9013111

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

RHOC GAPs stimulate RHOC GTPase activity

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The following GTPase activating proteins (GAPs) were shown to bind RHOC and stimulate its GTPase activity, resulting in GTP to GDP hydrolysis and conversion of the active RHOC:GTP complex into the inactive RHOC:GDP complex, or they were shown to bind to the constitutively active RHOC mutant in the high throughput screen conducted by Bagci et al. 2020, without testing for activation of RHOC GTPase activity (as indicated):
ARHGAP1 (Amin et al. 2016; supported by Bagci et al. 2020)
ARHGAP5 (Kusama et al. 2006; supported by Bagci et al. 2020)
ARHGAP18 (Chang et al. 2014)
ARHGAP26 (Amin et al. 2016)
DLC1 (Healy et al. 2008; Amin et al. 2016)
MYO9B (Graf et al. 2000; supported by Bagci et al. 2020)
RACGAP1 (Amin et al. 2016; supported by Bagci et al. 2020)
STARD13 (Amin et al. 2016)

The following GAPs were shown to bind RHOC and stimulate its GTPase activity in some but not all studies, or only their binding to the constitutively active RHOC mutant was shown without testing for activation of RHOC GTPase activity, and they are annotated as candidate RHOC GAPs:
ABR (Amin et al. 2016: RHOC directed GAP activity; Bagci et al. 2020: no binding to active RHOC)
ARHGAP21 (Lazarini et al. 2013: RHOC directed GAP activity; Bagci et al. 2020: no binding to active RHOC)
ARHGAP32 (Bagci et al. 2020: binding to active RHOC)
ARHGAP35 (Amin et al. 2016: RHOC directed GAP activity; Bagci et al. 2020: no binding to active RHOC)
ARHGAP39 (Bagci et al. 2020: binding to active RHOC)
BCR (Bagci et al. 2020: binding to active RHOC)
DEPDC1B (Bagci et al. 2020: binding to active RHOC)
OPHN1 (Amin et al. 2016: RHOC directed GAP activity; Bagci et al. 2020: no binding to active RHOC)
PIK3R1 (Bagci et al. 2020: binding to active RHOC)

The following GAPs do not act on RHOC or do not bind to the constitutively active RHOC mutant:
ARAP2 (Yoon et al. 2006; Bagci et al. 2020: no binding to active RHOC)
ARAP3 (Bagci et al. 2020: no binding to active RHOC)
ARHGAP12 (Bagci et al. 2020: no binding to active RHOC)
ARHGAP17 (Amin et al. 2016; Bagci et al. 2020: no binding to active RHOC)
ARHGAP29 (Bagci et al. 2020: no binding to active RHOC)
ARHGAP31 (Bagci et al. 2020: no binding to active RHOC)
ARHGAP42 (Bagci et al. 2020: no binding to active RHOC)
MYO9A (Bagci et al. 2020: no binding to active RHOC)
OCRL (Erdmann et al. 2006;Lichter Konecki et al. 2006; Bagci et al. 2020: no binding to active RHOC)
PIK3R2 (Bagci et al. 2020: no binding to active RHOC)
SRGAP2 (Bagci et al. 2020: no binding to active RHOC)
STARD8 (Amin et al. 2016)
SYDE1 (Bagci et al. 2020: no binding to active RHOC)

Literature References

PubMed ID	Title	Journal	Year
17932950	DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms Kim, TY, Shutes, A, Healy, KD, Juliano, RL, Hodgson, L, Harden, TK, Bang, YJ, Der, CJ, Maddileti, S, Hahn, KM	Mol. Carcinog.	2008
15107133	Scambio, a novel guanine nucleotide exchange factor for Rho Groffen, J, Heisterkamp, N, Senadheera, D, Haataja, L, Curtis, C, Hemmeryckx, B	Mol. Cancer	2004
27481945	Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins: A SYSTEMATIC APPROACH TOWARD SELECTIVE INACTIVATION OF RHO FAMILY PROTEINS Ahmadian, MR, Somlyo, AV, Amin, E, Koessmeier, KT, Jaiswal, M, Dvorsky, R, Reis, K, Derewenda, U, Nouri, K, Aspenström, P	J. Biol. Chem.	2016
16896804	Gef10--the third member of a Rho-specific guanine nucleotide exchange factor subfamily with unusual protein architecture Winkler, S, Mohl, M, Lutz, S, Wieland, T	Naunyn Schmiedebergs Arch. Pharmacol.	2006
16777452	The effect of missense mutations in the RhoGAP-homology domain on ocrl1 function Nussbaum, RL, Lichter-Konecki, U, Suchy, SF, Farber, LW, Cronin, JS	Mol. Genet. Metab.	2006
23200924	ARHGAP21 is a RhoGAP for RhoA and RhoC with a role in proliferation and migration of prostate adenocarcinoma cells Ridley, AJ, Machado-Neto, JA, Saad, ST, Verjovski-Almeida, S, Barcellos, KS, Lazarini, M, Traina, F, Brandão, MM, Moreira, YB	Biochim. Biophys. Acta	2013
7721814	Direct involvement of the small GTP-binding protein Rho in lbc oncogene function Olson, MF, Cerione, RA, Toksoz, D, Hall, A, Zheng, Y	J. Biol. Chem.	1995
11207612	Functional role for the class IX myosin myr5 in epithelial cell infection by Shigella flexneri Böwe, C, Bähler, M, Hilpelä, P, Adam, T, Graf, B	Cell. Microbiol.	2000
21454492	Mechanistic insights into specificity, activity, and regulatory elements of the regulator of G-protein signaling (RGS)-containing Rho-specific guanine nucleotide exchange factors (GEFs) p115, PDZ-RhoGEF (PRG), and leukemia-associated RhoGEF (LARG) Cirstea, IC, Ahmadian, MR, Uhlenbrock, K, Jaiswal, M, Dvorsky, R, Gremer, L, Haeusler, LC	J. Biol. Chem.	2011
16776779	Inactivation of Rho GTPases by p190 RhoGAP reduces human pancreatic cancer cell invasion and metastasis Endo, H, Nakamura, H, Tatsuta, M, Kusama, T, Inoue, M, Mukai, M, Ishikawa, O	Cancer Sci.	2006
17077126	ARAP2 effects on the actin cytoskeleton are dependent on Arf6-specific GTPase-activating-protein activity and binding to RhoA-GTP Casanova, JE, Randazzo, PA, Cuthbert, EJ, Davis, KK, Miura, K, Yoon, HY, Ahvazi, B	J. Cell. Sci.	2006
25425145	ARHGAP18: an endogenous inhibitor of angiogenesis, limiting tip formation and stabilizing junctions Gamble, JR, Powter, EE, Bower, NI, Coleman, PR, Jolly, CJ, Ting, KK, Rinkwitz, S, Lay, AJ, Chang, GH, Formaz-Preston, A, Zhao, Y, Vadas, MA, Becker, TS, Hogan, BM	Small GTPases	2014
19713215	Regulation of immature dendritic cell migration by RhoA guanine nucleotide exchange factor Arhgef5 Lehmann, D, Gan, X, Wang, P, Wang, Z, Li, L, Smrcka, AV, Iwasaki, A, Wu, D, Cohn, L, Kumamoto, Y	J. Biol. Chem.	2009
17765681	A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway Paradise, S, Zoncu, R, Lee, S, Mao, Y, Biemesderfer, D, McCrea, HJ, Toomre, D, De Camilli, P, Erdmann, KS, Modregger, J	Dev. Cell	2007
22673745	Divergence of Rho residue 43 impacts GEF activity Quinn, CV, Goetzinger, C, Farley, J, Sloan, CM, Ellerbroek, SM, Peters, JP, Wernli, M, DeMali, KA	Small GTPases	2012
23255595	Deciphering the molecular and functional basis of Dbl family proteins: a novel systematic approach toward classification of selective activation of the Rho family proteins Ahmadian, MR, Jaiswal, M, Dvorsky, R	J. Biol. Chem.	2013
31871319	Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms Tran, V, Gingras, AC, Elkholi, IE, Robert, A, Boulais, J, Faubert, D, Dubé, N, Hipfner, DR, Cote, JF, Lin, ZY, Bagci, H, Sriskandarajah, N, Thibault, MP	Nat. Cell Biol.	2020
16112081	GrinchGEF--a novel Rho-specific guanine nucleotide exchange factor Winkler, S, Mohl, M, Lutz, S, Wieland, T	Biochem. Biophys. Res. Commun.	2005
22911862	Identification of a novel actin-binding domain within the Rho guanine nucleotide exchange factor TEM4 Der, CJ, Rossman, KL, Mitin, N	PLoS ONE	2012