RhoG signals in parallel with Rac1 and Cdc42

Krister Wennerberg; Shawn M Ellerbroek; Rong-Yu Liu; Antoine E Karnoub; Keith Burridge; Channing J Der

doi:10.1074/jbc.M203816200

RhoG signals in parallel with Rac1 and Cdc42

Krister Wennerberg, Shawn M Ellerbroek, Rong-Yu Liu, Antoine E Karnoub, Keith Burridge, Channing J Der

81 Citations (Scopus)

Abstract

RhoG is a member of the Rho family of small GTPases and shares high sequence identity with Rac1 and Cdc42. Previous studies suggested that RhoG mediates its effects through activation of Rac1 and Cdc42. To further understand the mechanism of RhoG signaling, we studied its potential activation pathways, downstream signaling properties, and functional relationship to Rac1 and Cdc42 in vivo. First, we determined that RhoG was regulated by guanine nucleotide exchange factors that also activate Rac and/or Cdc42. Vav2 (which activates RhoA, Rac1, and Cdc42) and to a lesser degree Dbs (which activates RhoA and Cdc42) activated RhoG in vitro. Thus, RhoG may be activated concurrently with Rac1 and Cdc42. Second, some effectors of Rac/Cdc42 (IQGAP2, MLK-3, PLD1), but not others (e.g. PAKs, POSH, WASP, Par-6, IRSp53), interacted with RhoG in a GTP-dependent manner. Third, consistent with this differential interaction with effectors, activated RhoG stimulated some (JNK and Akt) but not other (SRF and NF-kappaB) downstream signaling targets of activated Rac1 and Cdc42. Finally, transient transduction of a tat-tagged Rac1(17N) dominant-negative fusion protein inhibited the induction of lamellipodia by the Rac-specific activator, Tiam1, but not by activated RhoG. Together, these data argue that RhoG function is mediated by signals independent of Rac1 and Cdc42 activation and instead by direct utilization of a subset of common effectors.

Original language	English
Journal	The Journal of Biological Chemistry
Volume	277
Issue number	49
Pages (from-to)	47810-7
Number of pages	8
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.M203816200
Publication status	Published - 6 Dec 2002
Externally published	Yes

Keywords

3T3 Cells
Animals
DNA, Complementary/metabolism
Enzyme Activation
Epitopes
GTP Phosphohydrolases/metabolism
Gene Library
Green Fluorescent Proteins
Guanine Nucleotide Exchange Factors/metabolism
Guanosine Triphosphate/metabolism
Humans
Luminescent Proteins/metabolism
Mice
Microscopy, Fluorescence
NF-kappa B/metabolism
Protein Binding
Protein Structure, Tertiary
Signal Transduction
Time Factors
Transfection
cdc42 GTP-Binding Protein/metabolism
rac1 GTP-Binding Protein/metabolism
rho GTP-Binding Proteins
rhoA GTP-Binding Protein/metabolism

Access to Document

10.1074/jbc.M203816200

Cite this

@article{df34b769dc9e4726bde0a4d547b1ac8c,

title = "RhoG signals in parallel with Rac1 and Cdc42",

abstract = "RhoG is a member of the Rho family of small GTPases and shares high sequence identity with Rac1 and Cdc42. Previous studies suggested that RhoG mediates its effects through activation of Rac1 and Cdc42. To further understand the mechanism of RhoG signaling, we studied its potential activation pathways, downstream signaling properties, and functional relationship to Rac1 and Cdc42 in vivo. First, we determined that RhoG was regulated by guanine nucleotide exchange factors that also activate Rac and/or Cdc42. Vav2 (which activates RhoA, Rac1, and Cdc42) and to a lesser degree Dbs (which activates RhoA and Cdc42) activated RhoG in vitro. Thus, RhoG may be activated concurrently with Rac1 and Cdc42. Second, some effectors of Rac/Cdc42 (IQGAP2, MLK-3, PLD1), but not others (e.g. PAKs, POSH, WASP, Par-6, IRSp53), interacted with RhoG in a GTP-dependent manner. Third, consistent with this differential interaction with effectors, activated RhoG stimulated some (JNK and Akt) but not other (SRF and NF-kappaB) downstream signaling targets of activated Rac1 and Cdc42. Finally, transient transduction of a tat-tagged Rac1(17N) dominant-negative fusion protein inhibited the induction of lamellipodia by the Rac-specific activator, Tiam1, but not by activated RhoG. Together, these data argue that RhoG function is mediated by signals independent of Rac1 and Cdc42 activation and instead by direct utilization of a subset of common effectors.",

keywords = "3T3 Cells, Animals, DNA, Complementary/metabolism, Enzyme Activation, Epitopes, GTP Phosphohydrolases/metabolism, Gene Library, Green Fluorescent Proteins, Guanine Nucleotide Exchange Factors/metabolism, Guanosine Triphosphate/metabolism, Humans, Luminescent Proteins/metabolism, Mice, Microscopy, Fluorescence, NF-kappa B/metabolism, Protein Binding, Protein Structure, Tertiary, Signal Transduction, Time Factors, Transfection, cdc42 GTP-Binding Protein/metabolism, rac1 GTP-Binding Protein/metabolism, rho GTP-Binding Proteins, rhoA GTP-Binding Protein/metabolism",

author = "Krister Wennerberg and Ellerbroek, {Shawn M} and Rong-Yu Liu and Karnoub, {Antoine E} and Keith Burridge and Der, {Channing J}",

year = "2002",

month = dec,

day = "6",

doi = "10.1074/jbc.M203816200",

language = "English",

volume = "277",

pages = "47810--7",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

number = "49",

}

TY - JOUR

T1 - RhoG signals in parallel with Rac1 and Cdc42

AU - Wennerberg, Krister

AU - Ellerbroek, Shawn M

AU - Liu, Rong-Yu

AU - Karnoub, Antoine E

AU - Burridge, Keith

AU - Der, Channing J

PY - 2002/12/6

Y1 - 2002/12/6

N2 - RhoG is a member of the Rho family of small GTPases and shares high sequence identity with Rac1 and Cdc42. Previous studies suggested that RhoG mediates its effects through activation of Rac1 and Cdc42. To further understand the mechanism of RhoG signaling, we studied its potential activation pathways, downstream signaling properties, and functional relationship to Rac1 and Cdc42 in vivo. First, we determined that RhoG was regulated by guanine nucleotide exchange factors that also activate Rac and/or Cdc42. Vav2 (which activates RhoA, Rac1, and Cdc42) and to a lesser degree Dbs (which activates RhoA and Cdc42) activated RhoG in vitro. Thus, RhoG may be activated concurrently with Rac1 and Cdc42. Second, some effectors of Rac/Cdc42 (IQGAP2, MLK-3, PLD1), but not others (e.g. PAKs, POSH, WASP, Par-6, IRSp53), interacted with RhoG in a GTP-dependent manner. Third, consistent with this differential interaction with effectors, activated RhoG stimulated some (JNK and Akt) but not other (SRF and NF-kappaB) downstream signaling targets of activated Rac1 and Cdc42. Finally, transient transduction of a tat-tagged Rac1(17N) dominant-negative fusion protein inhibited the induction of lamellipodia by the Rac-specific activator, Tiam1, but not by activated RhoG. Together, these data argue that RhoG function is mediated by signals independent of Rac1 and Cdc42 activation and instead by direct utilization of a subset of common effectors.

AB - RhoG is a member of the Rho family of small GTPases and shares high sequence identity with Rac1 and Cdc42. Previous studies suggested that RhoG mediates its effects through activation of Rac1 and Cdc42. To further understand the mechanism of RhoG signaling, we studied its potential activation pathways, downstream signaling properties, and functional relationship to Rac1 and Cdc42 in vivo. First, we determined that RhoG was regulated by guanine nucleotide exchange factors that also activate Rac and/or Cdc42. Vav2 (which activates RhoA, Rac1, and Cdc42) and to a lesser degree Dbs (which activates RhoA and Cdc42) activated RhoG in vitro. Thus, RhoG may be activated concurrently with Rac1 and Cdc42. Second, some effectors of Rac/Cdc42 (IQGAP2, MLK-3, PLD1), but not others (e.g. PAKs, POSH, WASP, Par-6, IRSp53), interacted with RhoG in a GTP-dependent manner. Third, consistent with this differential interaction with effectors, activated RhoG stimulated some (JNK and Akt) but not other (SRF and NF-kappaB) downstream signaling targets of activated Rac1 and Cdc42. Finally, transient transduction of a tat-tagged Rac1(17N) dominant-negative fusion protein inhibited the induction of lamellipodia by the Rac-specific activator, Tiam1, but not by activated RhoG. Together, these data argue that RhoG function is mediated by signals independent of Rac1 and Cdc42 activation and instead by direct utilization of a subset of common effectors.

KW - 3T3 Cells

KW - Animals

KW - DNA, Complementary/metabolism

KW - Enzyme Activation

KW - Epitopes

KW - GTP Phosphohydrolases/metabolism

KW - Gene Library

KW - Green Fluorescent Proteins

KW - Guanine Nucleotide Exchange Factors/metabolism

KW - Guanosine Triphosphate/metabolism

KW - Humans

KW - Luminescent Proteins/metabolism

KW - Mice

KW - Microscopy, Fluorescence

KW - NF-kappa B/metabolism

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Signal Transduction

KW - Time Factors

KW - Transfection

KW - cdc42 GTP-Binding Protein/metabolism

KW - rac1 GTP-Binding Protein/metabolism

KW - rho GTP-Binding Proteins

KW - rhoA GTP-Binding Protein/metabolism

U2 - 10.1074/jbc.M203816200

DO - 10.1074/jbc.M203816200

M3 - Journal article

C2 - 12376551

SN - 0021-9258

VL - 277

SP - 47810

EP - 47817

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 49

ER -

RhoG signals in parallel with Rac1 and Cdc42

Abstract

Keywords

Access to Document

Fingerprint

Cite this