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Sphingosine Kinase Interacting Protein is an A-Kinase Anchoring Protein Specific for Type I cAMP-Dependent Protein Kinase
- Source :
- ChemBioChem. 11:963-971
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- 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 (PKA-R) with the versatile family of A-kinase-anchoring proteins (AKAPs). Most AKAPs bind avidly to PKA-RII, while some have dual specificity for both PKA-RI and PKA-RII; however, no mammalian PKA-RI-specific AKAPs have thus far been assigned. This has mainly been attributed to the observation that PKA-RI is more cytosolic than the more heavily compartmentalized PKA-RII. 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 PKA-RIalpha. 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 PKA-RI directly in mammalian heart and spleen tissue. Immunolocalization studies revealed that recombinant SPHKAP is expressed in the cytoplasm, where PKA-RIalpha also mainly resides. Alignment of SPHKAPs' amphipathic helix with peptide models of PKA-RI- or PKA-RII-specific anchoring domains shows that it has largely only PKA-RIalpha characteristics. Being the first mammalian PKA-RI-specific AKAP with cytosolic localization, SPHKAP is a very promising model for studying the function of the less explored cytosolic PKA-RI signaling nodes.
- Subjects :
- A-kinase-anchoring protein
endocrine system
Heart Ventricles
Protein subunit
Molecular Sequence Data
Sphingosine kinase
A Kinase Anchor Proteins
Mitogen-activated protein kinase kinase
Biology
Biochemistry
Interactome
Cell Line
Cyclic AMP
Humans
ASK1
Amino Acid Sequence
Protein kinase A
Molecular Biology
Adaptor Proteins, Signal Transducing
Kinase
Organic Chemistry
Recombinant Proteins
Protein Structure, Tertiary
Cell biology
Cyclic AMP-Dependent Protein Kinase Type I
Molecular Medicine
Sequence Alignment
Subjects
Details
- ISSN :
- 14394227
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- ChemBioChem
- Accession number :
- edsair.doi.dedup.....dc11942d0c21c68b31517c9f28fb771b