Striatin-interacting phosphatase and kinase complex (STRIPAK)

The Striatin-interacting phosphatase and kinase (STRIPAK) complex is a highly conserved, multicomponent supramolecular assembly that functions as a critical signaling hub in eukaryotic cells. It is organized around striatin family scaffolding proteins (STRN, STRN3, STRN4), which recruit the catalytic and structural subunits of protein phosphatase 2A (PP2A) along with various germinal center kinase III (GCKIII) and GCKIV family members. STRIPAK plays a central role in regulating major pathways such as Hippo, MAPK, and Ras signaling, thereby influencing cell growth, proliferation, apoptosis, and cytoskeleton dynamics. In oncology, dysregulation of STRIPAK components or the formation of oncogenic fusions, such as STRN-ALK, contributes to tumorigenesis, metastasis, and resistance to standard therapies. The complex is also implicated in non-oncological conditions including cardiovascular diseases, diabetes, and cerebral cavernous malformation. Therapeutic strategies currently focus on inhibiting its catalytic subunits with small molecules like LB100, disrupting protein-protein interactions with experimental peptides, or utilizing ALK inhibitors to target STRN-ALK fusions. However, drug development faces challenges due to the complex's widespread physiological roles and potential for paradoxical effects, such as the promotion of amoeboid migration in certain cancer contexts.

Other names

Striatin-interacting phosphatase and kinase complexStriatin family complexHippo-STRIPAK complexStriatin-centered supramolecular assembly

Inhibition of the catalytic phosphatase subunit (PP2A), disruption of protein-protein interactions between scaffolding and catalytic components, or targeted inhibition of oncogenic kinase fusions involving STRIPAK members (e.g., STRN-ALK).