Sphingosine kinase interacting protein is an A-kinase anchoring protein specific for type I cAMP-dependent protein kinase.

The compartmentalization of kinases and phosphatases plays an important role in the specificity of second-messenger-mediated signaling events. Localization of the cAMP-dependent protein kinase is mediated by interaction of its regulatory subunit with the versatile family of A-kinase-anchoring proteins (AKAPs). Most AKAPs bind avidly to while some have dual specificity for both and however, no mammalian AKAPs have thus far been assigned. This has mainly been attributed to the observation that duanyu1529-RI is more cytosolic than the more heavily compartmentalized Chemical proteomics screens of the cAMP interactome in mammalian heart tissue recently identified sphingosine kinase type 1-interacting protein (SKIP, SPHKAP) as a putative novel AKAP. Biochemical characterization now shows that SPHKAP can be considered as the first mammalian AKAP that preferentially binds to Recombinant human SPHKAP functions as an RI-specific AKAP that utilizes the characteristic AKAP amphipathic helix for interaction. Further chemical proteomic screening utilizing differential binding characteristics of specific cAMP resins confirms SPHKAPs endogenous specificity for duanyu1529-RI directly in mammalian heart and spleen tissue. Immunolocalization studies revealed that recombinant SPHKAP is expressed in the cytoplasm, where also mainly resides. Alignment of SPHKAPs' amphipathic helix with peptide models of or anchoring domains shows that it has largely only duanyu1529-RIalpha characteristics. Being the first mammalian duanyu1529-RI-specific AKAP with cytosolic localization, SPHKAP is a very promising model for studying the function of the less explored cytosolic duanyu1529-RI signaling nodes.

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