Signal transduction occurs by the reversible assembly of oligomeric protein 
complexes that include both enzymatic proteins and proteins without known 
enzymatic activity. These nonenzymatic components can serve as scaffolds or 
anchors and regulate the efficiency, specificity, and localization of the 
signaling pathway. Here we report the identification of MORG1 (mitogen-activated 
protein kinase organizer 1), a member of the WD-40 protein family that was 
isolated as a binding partner of the extracellular signal-regulated kinase (ERK) 
pathway scaffold protein MP1. MORG1 specifically associates with several 
components of the ERK pathway, including MP1, Raf-1, MEK, and ERK, and 
stabilizes their assembly into an oligomeric complex. MORG1 facilitates ERK 
activation when cells are stimulated with lysophosphatidic acid, phorbol 
12-myristate 13-acetate, or serum, but not in response to epidermal growth 
factor. Suppression of MORG1 by short interfering RNA leads to a marked 
reduction in ERK activity when cells are stimulated with serum. We propose that 
MORG1 is a component of a modular scaffold system that participates in the 
regulation of agonist-specific ERK signaling.