STE20

Hippo (MST) STE20 kinases, primarily MST1 (STK4) and MST2 (STK3), are evolutionarily conserved serine/threonine kinases that function as core regulators of the Hippo signaling pathway, controlling cell proliferation, differentiation, apoptosis, tissue homeostasis, and organ size determination^[1][2][3]. Mechanistically, activated MST1/2 form a kinase cascade with SAV1, MOB1, and LATS1/2, leading to phosphorylation-dependent inhibition of YAP/TAZ transcriptional coactivators and suppression of proliferative gene expression programs^[2][3][4]. Through this signaling architecture, MST1/2 act as central tumor suppressors that restrain hyperproliferation and tumorigenesis across multiple tissues, while coordinating crosstalk with pathways involved in development and cellular stress responses^[1][2]. In disease-relevant models, combined loss of MST1 and MST2 promotes excessive tissue growth and tumor formation, whereas restoration of downstream Hippo pathway activity counteracts these phenotypes^[1]. Beyond growth control, MST1/2 contribute to immune regulation by controlling immune-cell activation, migration, survival, differentiation, and homeostasis, highlighting functions that extend beyond canonical YAP regulation^[1][3]. Compared with related STE20 family kinases, MST1 and MST2 are the principal Hippo pathway initiators and display substantial functional redundancy in many tissues, although context-dependent specialization has been reported in immune and stress-response settings^[1][2]. For experimental applications, pharmacological inhibition of MST1/2 using small molecules such as XMU-MP-1 is widely employed to modulate Hippo pathway activity and investigate regeneration, proliferation, apoptosis, and tissue-repair mechanisms in cellular and animal models^[5].