XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. / Arthur, William T; Ellerbroek, Shawn M; Der, Channing J; Burridge, Keith; Wennerberg, Krister.

In: The Journal of Biological Chemistry, Vol. 277, No. 45, 08.11.2002, p. 42964-72.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Arthur, WT, Ellerbroek, SM, Der, CJ, Burridge, K & Wennerberg, K 2002, 'XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC', The Journal of Biological Chemistry, vol. 277, no. 45, pp. 42964-72. https://doi.org/10.1074/jbc.M207401200

APA

Arthur, W. T., Ellerbroek, S. M., Der, C. J., Burridge, K., & Wennerberg, K. (2002). XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. The Journal of Biological Chemistry, 277(45), 42964-72. https://doi.org/10.1074/jbc.M207401200

Vancouver

Arthur WT, Ellerbroek SM, Der CJ, Burridge K, Wennerberg K. XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. The Journal of Biological Chemistry. 2002 Nov 8;277(45):42964-72. https://doi.org/10.1074/jbc.M207401200

Author

Arthur, William T ; Ellerbroek, Shawn M ; Der, Channing J ; Burridge, Keith ; Wennerberg, Krister. / XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. In: The Journal of Biological Chemistry. 2002 ; Vol. 277, No. 45. pp. 42964-72.

Bibtex

@article{2af715ed88944e3bbbbc132d63e7b56d,
title = "XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC",
abstract = "Rho proteins cycle between an inactive, GDP-bound state and an active, GTP-bound state. Activation of these GTPases is mediated by guanine nucleotide exchange factors (GEFs), which promote GDP to GTP exchange. In this study we have characterized XPLN, a Rho family GEF. Like other Rho GEFs, XPLN contains a tandem Dbl homology and pleckstrin homology domain topography, but lacks homology with other known functional domains or motifs. XPLN protein is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. In vitro, XPLN stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42. Consistent with these data, XPLN preferentially associates with RhoA and RhoB. The specificity of XPLN for RhoA and RhoB, but not RhoC, is surprising given that they share over 85% sequence identity. We determined that the inability of XPLN to exchange RhoC is mediated by isoleucine 43 in RhoC, a position occupied by valine in RhoA and RhoB. When expressed in cells, XPLN activates RhoA and RhoB, but not RhoC, and stimulates the assembly of stress fibers and focal adhesions in a Rho kinase-dependent manner. We also found that XPLN possesses transforming activity, as determined by focus formation assays. In conclusion, here we describe a Rho family GEF that can discriminate between the closely related RhoA, RhoB, and RhoC, possibly giving insight to the divergent functions of these three proteins.",
keywords = "3T3 Cells, Amino Acid Sequence, Animals, Brain/metabolism, Cloning, Molecular, Focal Adhesions/physiology, Gene Library, Guanine Nucleotide Exchange Factors/chemistry, HeLa Cells, Humans, Kinetics, Leukemia, Myeloid, Mice, Molecular Sequence Data, Organ Specificity, Rabbits, Recombinant Proteins/chemistry, Rho Guanine Nucleotide Exchange Factors, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Transfection, ras Proteins, rho GTP-Binding Proteins/metabolism, rhoA GTP-Binding Protein/metabolism, rhoB GTP-Binding Protein/metabolism, rhoC GTP-Binding Protein",
author = "Arthur, {William T} and Ellerbroek, {Shawn M} and Der, {Channing J} and Keith Burridge and Krister Wennerberg",
year = "2002",
month = nov,
day = "8",
doi = "10.1074/jbc.M207401200",
language = "English",
volume = "277",
pages = "42964--72",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "45",

}

RIS

TY - JOUR

T1 - XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC

AU - Arthur, William T

AU - Ellerbroek, Shawn M

AU - Der, Channing J

AU - Burridge, Keith

AU - Wennerberg, Krister

PY - 2002/11/8

Y1 - 2002/11/8

N2 - Rho proteins cycle between an inactive, GDP-bound state and an active, GTP-bound state. Activation of these GTPases is mediated by guanine nucleotide exchange factors (GEFs), which promote GDP to GTP exchange. In this study we have characterized XPLN, a Rho family GEF. Like other Rho GEFs, XPLN contains a tandem Dbl homology and pleckstrin homology domain topography, but lacks homology with other known functional domains or motifs. XPLN protein is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. In vitro, XPLN stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42. Consistent with these data, XPLN preferentially associates with RhoA and RhoB. The specificity of XPLN for RhoA and RhoB, but not RhoC, is surprising given that they share over 85% sequence identity. We determined that the inability of XPLN to exchange RhoC is mediated by isoleucine 43 in RhoC, a position occupied by valine in RhoA and RhoB. When expressed in cells, XPLN activates RhoA and RhoB, but not RhoC, and stimulates the assembly of stress fibers and focal adhesions in a Rho kinase-dependent manner. We also found that XPLN possesses transforming activity, as determined by focus formation assays. In conclusion, here we describe a Rho family GEF that can discriminate between the closely related RhoA, RhoB, and RhoC, possibly giving insight to the divergent functions of these three proteins.

AB - Rho proteins cycle between an inactive, GDP-bound state and an active, GTP-bound state. Activation of these GTPases is mediated by guanine nucleotide exchange factors (GEFs), which promote GDP to GTP exchange. In this study we have characterized XPLN, a Rho family GEF. Like other Rho GEFs, XPLN contains a tandem Dbl homology and pleckstrin homology domain topography, but lacks homology with other known functional domains or motifs. XPLN protein is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. In vitro, XPLN stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42. Consistent with these data, XPLN preferentially associates with RhoA and RhoB. The specificity of XPLN for RhoA and RhoB, but not RhoC, is surprising given that they share over 85% sequence identity. We determined that the inability of XPLN to exchange RhoC is mediated by isoleucine 43 in RhoC, a position occupied by valine in RhoA and RhoB. When expressed in cells, XPLN activates RhoA and RhoB, but not RhoC, and stimulates the assembly of stress fibers and focal adhesions in a Rho kinase-dependent manner. We also found that XPLN possesses transforming activity, as determined by focus formation assays. In conclusion, here we describe a Rho family GEF that can discriminate between the closely related RhoA, RhoB, and RhoC, possibly giving insight to the divergent functions of these three proteins.

KW - 3T3 Cells

KW - Amino Acid Sequence

KW - Animals

KW - Brain/metabolism

KW - Cloning, Molecular

KW - Focal Adhesions/physiology

KW - Gene Library

KW - Guanine Nucleotide Exchange Factors/chemistry

KW - HeLa Cells

KW - Humans

KW - Kinetics

KW - Leukemia, Myeloid

KW - Mice

KW - Molecular Sequence Data

KW - Organ Specificity

KW - Rabbits

KW - Recombinant Proteins/chemistry

KW - Rho Guanine Nucleotide Exchange Factors

KW - Sequence Alignment

KW - Sequence Homology, Amino Acid

KW - Substrate Specificity

KW - Transfection

KW - ras Proteins

KW - rho GTP-Binding Proteins/metabolism

KW - rhoA GTP-Binding Protein/metabolism

KW - rhoB GTP-Binding Protein/metabolism

KW - rhoC GTP-Binding Protein

U2 - 10.1074/jbc.M207401200

DO - 10.1074/jbc.M207401200

M3 - Journal article

C2 - 12221096

VL - 277

SP - 42964

EP - 42972

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 45

ER -

ID: 199433542