| | |  | | | | Record from Web of Science® | | | | | | |
| Vav2 is an activator of Cdc42, Rac1, and RhoA |
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| Author(s): Abe K, Rossman KL, Liu B, Ritola KD, Chiang D, Campbell SL, Burridge K, Der CJ |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 275 Issue: 14 Pages: 10141-10149 Published: APR 7 2000 |
| Times Cited: 112 References: 50 |
| Abstract: Vav and Vav2 are members of the Dbl family of proteins that act as guanine nucleotide exchange factors (GEFs) for Rho family proteins. Whereas Vav expression is restricted to cells of hematopoietic origin, Vav2 is widely expressed. Although Vav and Vav2 share highly related structural similarities and high sequence identity in their Dbl homology domains, it has been reported that they are active GEFs with distinct substrate specificities toward Rho family members. Whereas Vav displayed GEF activity for Rac1, Cdc42, RhoA, and RhoG, Vav2 was reported to exhibit GEF activity for RhoA, RhoB, and RhoG but not for Rad or Cdc42. Consistent with their distinct substrate targets, it was found that constitutively activated versions of Vav and Vav2 caused distinct transformed phenotypes when expressed in NIH 3T3 cells. In contrast to the previous findings, we found that Vav2 can act as a potent GEF for Cdc42, Rac1, and RhoA in vitro. Furthermore, we found that NH2-terminally truncated and activated Vav and Vav2 caused indistinguishable transforming actions in NIH 3T3 cells that required Cdc42, Rad, and RhoA function. In addition, like Vav and Rad, we found that Vav2 activated the Jun NH2-terminal kinase cascade and also caused the formation of lamellipodia and membrane ruffles in NIH 3T3 cells. Finally, Vav2-transformed NIH 3T3 cells showed up-regulated levels of Rac-GTP. We conclude that Vav2 and Vav share overlapping downstream targets and are activators of multiple Rho family proteins. Therefore, Vav2 may mediate the same cellular consequences in nonhematopoietic cells as Vav does in hematopoietic cells. |
| Document Type: Article |
| Language: English |
| Reprint Address: Der, CJ (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pharmacol, CB 7295, Chapel Hill, NC 27599 USA |
Addresses:
1. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pharmacol, Chapel Hill, NC 27599 USA
2. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
3. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 302BT |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |