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The Erk non-Smad pathway. TGF-β can induce phosphorylation of tyrosine residues on both type I and type II receptors and/or on Shc. The phosphorylated tyrosines are capable of recruiting Grb2/Sos to activate Erk through Ras, Raf, and their downstream MAPK cascades. Erk then regulates target gene transcription through its downstream transcription factors in conjunction with Smads to control EMT. Erk can also inhibit R-Smad activities through phosphorylation of R-Smads.
