Sterile 20-like kinase family (STE20) (STE20)

The Sterile 20-like (STE20) kinase family is a large and diverse group of serine/threonine kinases that act as essential upstream regulators in multiple signaling cascades, including the mitogen-activated protein kinase (MAPK) and Hippo pathways (Delpire, 2009). These kinases are structurally categorized into two main subfamilies: the p21-activated kinases (PAKs) and the germinal center kinases (GCKs), which collectively govern fundamental cellular processes such as cytoskeletal organization, cell cycle progression, and apoptosis (Strange et al., 2006). Dysregulation of STE20 family members is frequently observed in various human diseases, particularly in cancer, where they promote tumor growth, metastasis, and immune evasion (Dan et al., 2001). For instance, PAKs are often overexpressed in solid tumors, while GCK members like MST1/2 are central to the Hippo pathway's role in organ size control and tumor suppression (Ling et al., 2008). Due to their pivotal roles in disease-driving signaling networks, several STE20 family members have emerged as attractive therapeutic targets, with small-molecule inhibitors like HPK1 and PAK inhibitors currently undergoing clinical and preclinical evaluation (Cansado et al., 2022). Beyond oncology, STE20 kinases are also implicated in neurodegenerative diseases and metabolic disorders, further expanding their therapeutic potential (Larhammar et al., 2017). Therapeutic strategies primarily focus on ATP-competitive small molecules, although challenges such as off-target toxicity and pathway redundancy remain significant hurdles in drug development (Record et al., 2010).

Other names

STE20-related kinasesSterile 20 kinasesMAP kinase kinase kinase kinase familyGCK familyPAK family

ATP-competitive inhibition of the kinase domain, preventing phosphorylation of downstream substrates in the MAPK or Hippo pathways.