Striatin-interacting phosphatase and kinase complex (STRIPAK) (STRIPAK)

The Striatin-interacting phosphatase and kinase (STRIPAK) complex is a highly conserved supramolecular assembly that serves as a critical signaling hub in eukaryotic cells (Hwang & Pallas, 2014, PMID: 24531451). It is organized around a striatin family scaffold protein (STRN, STRN3, or STRN4) which bridges the catalytic and regulatory subunits of protein phosphatase 2A (PP2A) with various kinases, most notably the Germinal Center Kinase III (GCKIII) family members like MST3, MST4, and STK25 (Shi et al., 2016, PMID: 27138231). STRIPAK plays a pivotal role in regulating diverse cellular processes including the Hippo signaling pathway, MAPK signaling, cell polarity, and Golgi apparatus organization (Madsen et al., 2015, PMID: 25838486). Dysregulation of the STRIPAK complex is implicated in several pathologies, including Cerebral Cavernous Malformations (CCM) caused by mutations in the CCM3 (PDCD10) component, and various malignancies where it promotes tumor growth and metastasis (Tang et al., 2019, PMID: 31110054). While no drugs currently target the entire complex as a single entity, individual components like PP2A and GCKIII kinases are active targets for therapeutic intervention. For instance, PP2A inhibitors like LB-100 and activators like Fingolimod modulate the complex's phosphatase activity, while experimental small molecules are being developed to disrupt specific protein-protein interactions within the assembly to treat cancer and vascular diseases (Neat et al., 2022, PMID: 35411056).

Other names

STRIPAK complexStriatin-PP2A complexStriatin-containing phosphatase and kinase complexStriatin-interacting phosphatase and kinase

Modulation of protein phosphatase 2A (PP2A) activity, inhibition of Germinal Center Kinase III (GCKIII) activity, and disruption of protein-protein interactions within the scaffold assembly.