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 -