Sphingosine kinase type 1-interacting protein (SPHKAP)

Sphingosine kinase type 1-interacting protein (SPHKAP, also called SKIP) is an anchoring protein that binds specifically and preferentially to the type I regulatory subunit of cAMP-dependent protein kinase (PKA type I), facilitating its subcellular localization and the spatial organization of cAMP signaling. Unlike most other AKAPs that interact with PKA type II, SPHKAP is the first known mammalian AKAP that is RI-specific, primarily localizing PKA-RIα in the cytoplasm[2][5][8]. In addition to its role in signal compartmentalization, SPHKAP modulates the activity of sphingosine kinase 1 (SPHK1), suggesting it acts as a molecular link between cAMP and sphingosine signaling pathways[4][5]. Recent research indicates that SPHKAP/SKIP is highly expressed in pancreatic β-cells, where it negatively regulates glucose-stimulated insulin secretion (GSIS) via a pathway that is distinct from classical cAMP-, PDE-, or SPHK-dependent pathways, potentially implicating it in the physiology of glucose homeostasis and diabetes[7]. There is currently no evidence that SPHKAP is targeted by any approved drugs, nor is it established as a direct therapeutic target.

Other names

Sphingosine kinase type 1-interacting proteinSPHK1 interactorAKAP domain containingA-kinase anchor protein SPHKAPSKIPKIAA1678