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Raf (c-Raf-1) is a cytoplasmic serine/threonine protein kinase and is a member of a family of proteins which are highly conserved from Drosophila to mammals. Raf has a critical role in the response to many growth factors including: EGF, PDGF, insulin, IL-2, IL-3, CSF-1, and GM-CSF. Raf can directly interact with Ras-GTP and subsequently become activated. Thus Raf plays a prominent role in the Ras signaling pathway by transferring a signal from Ras which has been activated by growth factor receptor-stimulated tyrosine kinase activity. This leads to the stimulation and activation of a number of other cytoplasmic serine/threonine kinases. Raf regulates the MAP kinase pathway by phosphorylating and activating MEK, which then phosphorylates and activates MAP kinase (ERK). ERK then phosphorylates and activates Rsk. Raf activity can also be regulated independently of Ras. Cyclic AMP (cAMP) activation of protein kinase A (PKA) can inhibit growth factor stimulation of Raf.