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The mitogen-activated protein (MAP) kinases are a large family of proline-directed, serine/threonine kinases that require tyrosine and threonine phosphorylation of a TxY motif in the activation loop for activation through a phosphorylation cascade involving a MAPKKK, MAPKK and MAPK, often referred to as the MAP kinase module. Three separate such modules have been identified, based on the TxY motif of the MAP kinase and the dual-specificity kinases that strictly phosphorylate their specific TxY sequence. They are the extracellular signal regulated kinases (ERKs), c-jun N-terminal kinases (JNKs) and p38 MAPKs. The ERKs are mainly associated with proliferation and differentiation while the JNKs and p38MAP kinases regulate responses to cellular stresses.