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Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade.

Authors: Buchsbaum, RJ  Connolly, BA  Feig, LA 
Citation: Buchsbaum RJ, etal., Mol Cell Biol. 2002 Jun;22(12):4073-85.
Pubmed: (View Article at PubMed) PMID:12024021

Tiam1 and Ras-GRF1 are guanine nucleotide exchange factors (GEFs) that activate the Rac GTPase. The two GEFs have similar N-terminal regions containing pleckstrin homology domains followed by coiled-coils and additional sequences that function together to allow regulated GEF activity. Here we show that this N-terminal region of both proteins binds to the scaffold protein IB2/JIP2. IB2/JIP2 is a scaffold for the p38 mitogen-activated protein (MAP) kinase cascade because it binds to the Rac target MLK3, the MAP kinase kinase MKK3, and the p38 MAP kinase. Expression of IB2/JIP2 in cells potentiates the ability of Tiam1 or Ras-GRF1 to activate the p38 MAP kinase cascade but not the Jnk MAP kinase cascade. In addition, Tiam1 or Ras-GRF1 binding to IB2/JIP2 increases the association of the components of the p38 MAP kinase signaling cassette with IB2/JIP2 in cells and activates scaffold-associated p38. These findings imply that Tiam1 and Ras-GRF1 can contribute to Rac signaling specificity by their ability to form a complex with a scaffold that binds components of one of the many known Rac effector pathways.


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RGD Object Information
RGD ID: 2302280
Created: 2008-12-08
Species: All species
Last Modified: 2008-12-08
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.