The duration, magnitude and sub-cellular compartmentalization of ERK Torin 1 activation elicits different cellular outcomes leading to functional activation, proliferation, differentiation, migration, or survival. For instance, in PC12 cells, sustained ERK activation causes differentiation, strong ERK activation leads to differentiation in normal cells and survival in carcinoma cells, whereas weak ERK activation results in proliferation in normal cells and apoptosis in carcinoma cells. These outcomes are collectively regulated by a number of regulators under different physiological conditions and disease states, such as tumorigenesis, cardiovascular disease, and urinary bladder dysfunction. One important class of ERK regulators are scaffold proteins that compartmentalize and spatio-temporally control ERK Wortmannin signaling to regulate signaling strength and duration, confer signaling specificity, diversify signaling kinetics, and prevent signaling activation by irrelevant stimuli. Scaffold proteins perform these tasks by assembling signaling components, localizing signaling molecules, coordinating positive and negative feedback, and insulating activated signaling molecules from inactivation. Two scaffold proteins, Kinase Suppressor of Ras and MEK Partner 1, are involved in the regulation of EGF-induced ERK signaling in PC12 and other cells. KSR is a multi-domain protein that binds Raf-1, MEK, ERK, and several other proteins. In resting cells, it is sequestered in the cytosol by 14-3-3 proteins. In response to EGF stimulation, is released from 14-3-3 and recruited to the plasma membrane to scaffold Raf-1, MEK1/2 and ERK1/2 and to subsequently facilitate Ras activation of the Raf-MEK-ERK module. On the other hand, MP1 is a widely expressed small scaffold protein that is recruited to late endosomes by the adaptor protein p14, where it promotes the assembly and interaction of MEK1 and ERK1. Upon stimulation by the internalized activated cell surface receptors that are trafficked to the late endosomes, MP1 facilitates Ras activation of the MEK1-ERK1 module there. Some important aspects and functional implications of the collective actions of these two scaffold proteins on ERK signaling have been studied. It has been suggested that sustained ERK activation may require coordinated control by KSR and the MP1- p14 complex to facilitate continued signaling from the plasma membrane to late endosomes, with KSR supporting the proliferative and transforming functions of ERK signaling and MP1 converting low MEK activity into sustained ERK activation. Overexpression of both MP1 and KSR can lead to different responses, depending on the relative stoichiometry of the individual components. For instance, overexpression of BKSR in PC12 cells, a neuronal-specific isoform of KSR, switches EGF signaling from a brief proliferative signal to a sustained differentiation signal.