| Mammalian sterile 20‑like kinase 3 (MST3, also termed STK24) is a Ste20‑related serine/threonine kinase that belongs to the germinal center kinase III subfamily and functions as a signaling node linking stress and polarity cues to cytoskeletal organization, cell migration, and cell death pathways. The protein contains an N‑terminal catalytic domain with the conserved HRD and DFG motifs required for kinase activity and a C‑terminal regulatory region with docking sequences for STRIPAK core subunits, endothelial polarity regulators, and other scaffolding proteins, and it is activated by phosphorylation within the activation loop and by release from STRIPAK‑mediated inhibition. MST3 localizes to the cytoplasm, Golgi region, and nucleus and associates with cytoskeletal and polarity complexes through interactions with CCM3 (PDCD10), STRNs, and other PP2A‑containing STRIPAK components, which position the kinase at sites where it can phosphorylate substrates involved in actin and microtubule remodeling and vesicular trafficking. MST3 phosphorylates and regulates proteins such as NDR family kinases and actin‑linked effectors and participates in cascades related to the Hippo pathway, where it contributes to NDR/LATS‑type kinase activation and to the control of proliferation, apoptosis, and junctional organization in epithelial and endothelial contexts. The kinase also modulates Rho family and p38/JNK MAPK–associated signaling modules through effects on cytoskeletal regulators and stress‑responsive targets, placing MST3 in pathways that integrate mechanical and oxidative inputs with changes in cell shape, motility, and survival. MST3 expression is detected in brain, heart, liver, and skeletal muscle, and its activity influences neuronal morphology, axonal outgrowth, and dendritic architecture through regulation of cytoskeletal dynamics and polarity complexes, linking this kinase to neuronal connectivity and vulnerability to apoptotic or degenerative signals. In epithelial and endothelial systems, MST3 contributes to barrier and polarity control and participates in CCM3–STRIPAK–MST3 axes that affect vascular integrity and lumen formation. Across tumors, altered MST3 expression or localization associates with changes in migration, invasion, and apoptosis. |
