MAP2K1 and neoplasm: 281,282 Following TGF-β-induced Ser or tyrosine phosphorylation of the type I TGF-β receptor, ShcA recruits GRB2 and SOS to activate ERK1/2 through RAS, RAF, and MEK1/2.281,283 Other signaling molecules, such as integrin, Notch, Wnt, TNF-α, long non-coding (lnc) RNA, and EGF, synergize with TGF-β signaling to promote tumor invasion and metastasis.284–290 Many studies suggest the existence of functional connections between TGF-β and RAS–RAF signaling in tumorigenesis.