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Titolo:
The insert region of RhoA is essential for Rho kinase activation and cellular transformation
Autore:
Zong, H; Kaibuchi, K; Quilliam, LA;
Indirizzi:
Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USAIndiana Univ Indianapolis IN USA 46202 l Biol, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 ol Ctr, Indianapolis, IN 46202 USA Nagoya Univ, Dept Cell Pharmacol, Grad Sch Med, Showa Ku, Aichi 4668550, Japan Nagoya Univ Aichi Japan 4668550 Sch Med, Showa Ku, Aichi 4668550, Japan
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 16, volume: 21, anno: 2001,
pagine: 5287 - 5298
SICI:
0270-7306(200108)21:16<5287:TIRORI>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIN STRESS FIBERS; BINDING PROTEIN-RHO; RAS TRANSFORMATION; CRYSTAL-STRUCTURE; FOCAL ADHESIONS; EFFECTOR REGION; FAMILY GTPASES; CDC42 REQUIRES; GTP ANALOG; CYTOSKELETON;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Quilliam, LA Indiana Univ, Sch Med, Dept Biochem & Mol Biol, 635 Barnhill Dr,MS-4053, Indianapolis, IN 46202 USA Indiana Univ 635 Barnhill Dr,MS-4053Indianapolis IN USA 46202
Citazione:
H. Zong et al., "The insert region of RhoA is essential for Rho kinase activation and cellular transformation", MOL CELL B, 21(16), 2001, pp. 5287-5298

Abstract

RhoA is involved in multiple cellular processes, including cytoskeletal organization, gene expression, and transformation. These processes are mediated by a variety of downstream effector proteins. However, which effectors are involved in cellular transformation and how these proteins are activatedfollowing interaction with Rho remains to be established. A unique featurethat distinguishes the Rho family from other Ras-related GTPases is the insert region, which may confer Rho-specific signaling events. Here we reportthat deletion of the insert region does not result in impaired effector binding. Instead, this insert deletion mutant (Rho Delta Ras, in which the insert helix has been replaced with loop 8 of Ras) acted in a dominant inhibitory fashion to block RhoA-induced transformation. Since Rho Delta Ras failed to promote stress fiber formation, we examined the ability of this mutant to bind to and subsequently activate Rho kinase. Surprisingly, Rho Delta Ras-GTP coprecipitated with Rho kinase but failed to activate it in vivo. These data suggested that the insert domain is not required for Rho kinase binding but plays a role in its activation. The constitutively active catalytic domain of Rho kinase did not promote focus formation alone or in the presence of Raf(340D) but cooperated with Rho Delta Ras to induce cellular transformation. This suggests that Rho kinase needs to cooperate with additional Rho effectors to promote transformation. Further, the Rho kinase catalytic domain reversed the inhibitory effect of Rho Delta Ras on Rho-induced transformation, suggesting that one of the downstream targets of Rho-inducedtransformation abrogated by Rho Delta Ras is indeed Rho kinase. In conclusion, we have demonstrated that the insert region of RhoA is required for Rho kinase activation but not for binding and that this kinase activity is required to induce morphologic transformation of NIH 3T3 cells.

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Documento generato il 04/07/20 alle ore 12:04:51