STK3 Gene: Function, Expression, and Role in Cancer | Hippo Pathway

STK3 (serine/threonine kinase 3), also known as MST2, is a core component of the Hippo signaling pathway. It phosphorylates and activates LATS1/2 kinases, leading to YAP1/TAZ cytoplasmic retention and inhibition of cell proliferation. STK3 also promotes apoptosis through caspase-dependent cleavage and activation of its kinase domain. The gene is located on chromosome 8q22.2 and encodes a 491-amino acid protein with an N-terminal kinase domain and a C-terminal regulatory SARAH domain.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Hippo signaling pathway (KEGG: hsa04390)

• Apoptosis (KEGG: hsa04210)

• Signaling by MST2 (Reactome: R-HSA-2028269)

STK3 (MST2) is a 491-amino acid serine/threonine kinase that functions as a core component of the Hippo tumor suppressor pathway. It contains an N-terminal catalytic kinase domain and a C-terminal SARAH domain required for homodimerization and interaction with SAV1. Upon activation by upstream signals, STK3 phosphorylates and activates LATS1/2, which in turn phosphorylate YAP1 and TAZ, promoting their cytoplasmic retention and degradation. STK3 also undergoes caspase-mediated cleavage during apoptosis, generating a constitutively active 36 kDa fragment that amplifies cell death signaling. Dysregulation of STK3 through mutation, deletion, or epigenetic silencing contributes to tumorigenesis in multiple cancer types.