The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 30 Jul 2003
doi: 10.1242/jcs.00689
Research Article
The C-terminal end of R-Ras contains a focal adhesion targeting signal
Johanna Furuhjelm
and
Johan Peränen*
* Author for correspondence (e-mail: johan.peranen{at}helsinki.fi)
R-Ras promotes cell adhesion and activation of integrins through a process that is yet unknown. We show here that active R-Ras (38V) promotes the formation of focal adhesions and a spread cell shape. By contrast, the dominant-negative mutant of R-Ras (43N) reduces the number of focal adhesions, leading to the formation of refractile cells. In adherent cells wild-type R-Ras, activated (38V) R-Ras and endogeous R-Ras were preferentially targeted to focal adhesions, whereas the dominant-negative mutant (43N) of R-Ras was excluded from these structures. Activated mutants of H-Ras and K-Ras were not found in focal adhesions. We dissected R-Ras to find out the determinants that are important for the targeting process. The outermost region in the N-terminus of R-Ras, as well as the intact proline-rich sequence in the C-terminus of R-Ras that mediates binding to Nck, were not essential. Mutating the potential palmitoylation site (C213A) of R-Ras results in depalmitoylation and accumulation of R-Ras in the Golgi. Using H-Ras/R-Ras, R-Ras/H-Ras and R-Ras/K-Ras hybrid molecules we showed that the C-termini (175-218 amino acids) of R-Ras contains the signal for focal adhesions targeting. Exchanging the hypervariable region of H-Ras to R-Ras inhibited the targeting of R-Ras to focal adhesions, whereas H-Ras obtained the ability to localize to focal adhesions after receiving the hypervariable region of R-Ras. This indicates that R-Ras targeting is mediated both by the nucleotide binding status as well as through a specific region in the C-terminus of R-Ras. These results indicate that targeting and activation of R-Ras are linked processes in the formation of focal adhesions.
This article has been cited by other articles:
|
|
|
|
 
G. Serini, L. Napione, M. Arese, and F. Bussolino
Besides adhesion: new perspectives of integrin functions in angiogenesis
Cardiovasc Res,
May 1, 2008;
78(2):
213 - 222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Lehto, M. I. Mayranpaa, T. Pellinen, P. Ihalmo, S. Lehtonen, P. T. Kovanen, P.-H. Groop, J. Ivaska, and V. M. Olkkonen
The R-Ras interaction partner ORP3 regulates cell adhesion
J. Cell Sci.,
March 1, 2008;
121(5):
695 - 705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Hodkinson, Paul. A. Elliott, Y. Lad, B. J. McHugh, A. C. MacKinnon, C. Haslett, and T. Sethi
Mammalian NOTCH-1 Activates beta1 Integrins via the Small GTPase R-Ras
J. Biol. Chem.,
September 28, 2007;
282(39):
28991 - 29001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Stasyk, N. Schiefermeier, S. Skvortsov, H. Zwierzina, J. Peranen, G. K. Bonn, and L. A. Huber
Identification of Endosomal Epidermal Growth Factor Receptor Signaling Targets by Functional Organelle Proteomics
Mol. Cell. Proteomics,
May 1, 2007;
6(5):
908 - 922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Takaya, T. Kamio, M. Masuda, N. Mochizuki, H. Sawa, M. Sato, K. Nagashima, A. Mizutani, A. Matsuno, E. Kiyokawa, et al.
R-Ras Regulates Exocytosis by Rgl2/Rlf-mediated Activation of RalA on Endosomes
Mol. Biol. Cell,
May 1, 2007;
18(5):
1850 - 1860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Hattula, J. Furuhjelm, J. Tikkanen, K. Tanhuanpaa, P. Laakkonen, and J. Peranen
Characterization of the Rab8-specific membrane traffic route linked to protrusion formation
J. Cell Sci.,
December 1, 2006;
119(23):
4866 - 4877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Dail, M. Richter, P. Godement, and E. B. Pasquale
Eph receptors inactivate R-Ras through different mechanisms to achieve cell repulsion
J. Cell Sci.,
April 1, 2006;
119(7):
1244 - 1254.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Nakada, J. A. Niska, N. L. Tran, W. S. McDonough, and M. E. Berens
EphB2/R-Ras Signaling Regulates Glioma Cell Adhesion, Growth, and Invasion
Am. J. Pathol.,
August 1, 2005;
167(2):
565 - 576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. P. Holly, M. K. Larson, and L. V. Parise
The Unique N-Terminus of R-Ras Is Required for Rac Activation and Precise Regulation of Cell Migration
Mol. Biol. Cell,
May 1, 2005;
16(5):
2458 - 2469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-W. Jeong, J.-O. Nam, and I.-S. Kim
The COOH-terminal End of R-Ras Alters the Motility and Morphology of Breast Epithelial Cells through Rho/Rho-Kinase
Cancer Res.,
January 15, 2005;
65(2):
507 - 515.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Serini and F. Bussolino
Common Cues in Vascular and Axon Guidance
Physiology,
December 1, 2004;
19(6):
348 - 354.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Colicelli
Human RAS Superfamily Proteins and Related GTPases
Sci. Signal.,
September 14, 2004;
2004(250):
re13 - re13.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2003
