Activation of the Mitogen-Activated Protein Kinase Pathway by Transforming Growth Factor-β

The mitogen-activated protein kinase (MAPK) superfamily includes three major subfamilies: extracellular signal-regulated kinase (Erks), c-Jun-N-terminal kinases (JNKs)/stress-activated protein kinases (SAPKs), and p38 kinases (1–3). Activation of MAPK requires the phosphorylation of both tyrosine (Y) and threonine (T) residues in a conserved motif: TEY for Erks, TPY for SAPKs, and TGY for p38 (1–3). These MAPKs, in turn, activate downstream substrates by phosphorylating a minimum consensus target sequence of Ser/Thr-Pro (1,2).