Figure 3.

The Hippo signalling pathway: key components and regulatory mechanisms. The Hippo pathway is highly conserved in Drosophila and in mammals, for example, mammalian sterile‐20‐like kinase (Mst) is the orthologue of Hippo, as listed in the diagram for comparison (right). The effector of the Hippo pathway is yes‐activated protein (YAP) and its paralogue transcriptional coactivator with PDZ‐binding motif (TAZ). As transcription co‐activator or co‐repressor, nuclear YAP/TAZ interacts with numerous transcriptional and epigenetic factors (indicated as “×”) controlling expression of target genes to promote cell proliferation and survival. A number of factors have been shown to regulate Mst1/Lats (large tumour suppressor homologue) kinase cascade through complex signalling mechanisms currently only partially understood (left, ➜, activation; ⊣ inhibition). Mst1/2 and Lats1/2 mediates YAP/TAZ phosphorylation/inactivation. This leads to cytoplasm retention of YAP/TAZ after binding with 14‐3‐3 or proteosomic degradation. ECM: extracellular matrix; MOB1/2: Mps one binder kinase activator like 1/2; mTORC: mammalian target of rapamycin complex; NF2: neurofibromin 2 (also known as merlin); PCMT1: protein‐L‐isoaspartate(D‐aspartate) O‐methyltransferase; PHLPP: PH domain and leucine rich repeat protein phosphatase; RAP2: Ras‐related GTPase; RASSF: Ras association domain‐containing proteins; RhoA: a small GTPase; Sav1: salvador homologue 1; TAOK: Tao kinase; TEADs: tea domain family members; β‐ or α‐AR: β‐ or α‐adrenoceptor