MST1

MST1 (STK4) is a serine/threonine kinase that functions as a core upstream regulator of the Hippo signaling pathway, where it controls cell proliferation, differentiation, apoptosis, and organ size homeostasis through kinase-dependent signaling networks^[1]. Mechanistically, activated MST1 forms signaling complexes that phosphorylate and activate LATS kinases, leading to inhibition of the transcriptional coactivator YAP and suppression of growth-promoting transcriptional programs^[1][2]. Beyond canonical Hippo signaling, MST1 also regulates cellular stress responses, redox homeostasis, immune cell activation, migration, adhesion, and apoptosis, highlighting its broad role in tissue homeostasis and disease biology^[1][3]. In disease contexts, genetic disruption of MST1 signaling contributes to immune dysfunction, while loss of MST1/MST2-mediated Hippo pathway activity is associated with hyperproliferation and tumorigenesis through dysregulated YAP activity^[1][4]. Experimental studies further demonstrate that MST1 deficiency causes primary immunodeficiency and impairs the maintenance of long-lived humoral immunity, establishing MST1-deficient models as valuable tools for investigating immune regulation and lymphocyte homeostasis^[4]. Compared with the closely related isoform MST2 (STK3), MST1 shares highly conserved kinase-domain architecture and overlapping Hippo pathway functions, although tissue-specific regulatory mechanisms and biological outputs can differ depending on cellular context^[2][5]. For experimental applications, MST1 activity is frequently investigated through modulation of the MST1/2-LATS-YAP signaling axis, which provides a widely used framework for studying tumor suppression, immune regulation, and Hippo pathway biology^[1][2].