2010
DOI: 10.1038/emboj.2010.20
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Unravelling the mechanism of dual-specificity GAPs

Abstract: The molecular mechanism by which dual-specificity RasGAPs of the Gap1 subfamily activate the GTP hydrolysis of both Rap and Ras is an unresolved phenomenon. RasGAPs and RapGAPs use different strategies to stimulate the GTPase reaction of their cognate G-proteins. RasGAPs contribute an arginine finger to orient through the Gln61 of Ras the nucleophilic water molecule. RapGAP contributes an asparagine (Asn thumb) into the active site to substitute for the missing Gln61. Here, by using steadystate kinetic assays … Show more

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Cited by 59 publications
(63 citation statements)
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“…Unlike Ras, Rap1 does not possess a glutamine at position 61, and RapGAPs do not employ a catalytic arginine residue (arginine finger) but provide an asparagine (asparagine thumb) to stimulate GTP hydrolysis. [12][13][14][15] Interestingly, the RasGAP domain of GAP1 IP4BP is sufficient to drive the hydrolysis of Rap1-GTP, 13 and recent studies suggest that the GAP domain of GAP1 IP4BP and RASAL can undergo conformational changes that enable them to interact with either Ras or Rap1. 15 Hence, both Ras and Rap1 GTPases might compete for GAP1 IP4BP and RASAL recruitment in cells, and the local concentration of Ras and Rap1 in any microenvironment might determine the biological activity of these GAPs.…”
Section: Gap1 M and Gap1 Ib4bpmentioning
confidence: 99%
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“…Unlike Ras, Rap1 does not possess a glutamine at position 61, and RapGAPs do not employ a catalytic arginine residue (arginine finger) but provide an asparagine (asparagine thumb) to stimulate GTP hydrolysis. [12][13][14][15] Interestingly, the RasGAP domain of GAP1 IP4BP is sufficient to drive the hydrolysis of Rap1-GTP, 13 and recent studies suggest that the GAP domain of GAP1 IP4BP and RASAL can undergo conformational changes that enable them to interact with either Ras or Rap1. 15 Hence, both Ras and Rap1 GTPases might compete for GAP1 IP4BP and RASAL recruitment in cells, and the local concentration of Ras and Rap1 in any microenvironment might determine the biological activity of these GAPs.…”
Section: Gap1 M and Gap1 Ib4bpmentioning
confidence: 99%
“…[41][42][43] Similarly, once the Ras binding domain of p120GAP is recruited to the membrane, it is transiently immobile to interact with H-and K-Ras-GTP. 54 Given that some full-length GAPs act differently compared to their GAP domains, 15 it is still to be determined if this mechanism also applies for fulllength p120GAP or other GAPs.…”
Section: Subcellular Localization Of Ras Signaling Complexesmentioning
confidence: 99%
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