MAP3K2 and cancer: For example, methylation of MAPK kinase kinase 2 (MAP3K2) at Lys260 prevents the binding of protein phosphatase 2A complex (a key negative regulator of the MAPK pathway), resulting in elevated MAP3K2 signaling and promotion of Ras-driven cancer.142 Mono-methylation of a crucial lysine within the nuclear export signal sequence of YAP, a key effector of the Hippo pathway, blocks its interaction with the nuclear exporter CRM1, which results in the retention of YAP in the nucleus and stimulates YAP-mediated transcription activity and tumorigenesis143 (Fig. 4b).