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Ras activates Raf, leading to the extracellular-regulated kinase (ERK)-mitogen-activated protein kinase pathway, which is involved in a variety of cellular, physiological, and pathological responses. Thus, regulators of this Ras-Raf interaction play crucial roles in these responses. In this study, we report a novel regulator of the Ras-Raf interaction named DA-Raf1. DA-Raf1 is a splicing isoform of A-Raf with a wider tissue distribution than A-Raf. It contains the Ras-binding domain but lacks the kinase domain, which is responsible for activation of the ERK pathway. As inferred from its structure, DA-Raf1 bound to activated Ras as well as M-Ras and interfered with the ERK pathway. The Ras-ERK pathway is essential for the negative regulation of myogenic differentiation induced by growth factors. DA-Raf1 served as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation. These results imply that DA-Raf1 is the first identified competent, intrinsic, dominant-negative antagonist of the Ras-ERK pathway.
Pubmed ID: 17535970 RIS Download
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Cell line COS-1 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line PC12 is a Cancer cell line with a species of origin Rattus norvegicus
View all literature mentionsCell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
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