Large tumor suppressor kinase 2 (LATS2) (LATS2)

Large tumor suppressor kinase 2 (LATS2) is a critical serine/threonine kinase and a central component of the Hippo signaling pathway, which governs organ size and tissue homeostasis by regulating cell proliferation and apoptosis (UniProt Q9NRM7). LATS2 is activated by upstream kinases MST1/2 and MAP4Ks, subsequently phosphorylating the oncoproteins YAP1 and TAZ to sequester them in the cytoplasm or trigger their degradation (PubMed: 21115479). In many human cancers, LATS2 function is lost through genetic deletion or epigenetic silencing, leading to uncontrolled YAP/TAZ activity and tumor progression (PubMed: 25214403). Conversely, in regenerative medicine, transient inhibition of LATS2 is being explored to promote tissue repair by stimulating cell proliferation (PubMed: 32554452). While direct clinical drugs targeting LATS2 are primarily in the discovery or preclinical stages, it remains a high-interest target for both oncology and regenerative therapies (PubMed: 30223175). Monitoring LATS2 expression and YAP1 localization serves as a vital biomarker strategy for assessing Hippo pathway integrity in clinical samples (PubMed: 12192039).

Other names

Serine/threonine-protein kinase LATS2KPMWarts-like kinase 2LATS homolog 2

LATS2 acts as a core component of the Hippo signaling pathway by phosphorylating and inactivating the transcriptional co-activators YAP1 and TAZ, thereby preventing their translocation to the nucleus and inhibiting the expression of genes promoting cell proliferation and survival (PubMed: 21115479).