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Deciphering the Role of Disulfide Bonds in RIalpha
Author(s) -
Day Michele Elizabeth,
Koller Antonius,
Taylor Susan S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1044.14
Subject(s) - mutant , dimer , protein subunit , disulfide bond , chemistry , protein kinase a , mutation , gene isoform , microbiology and biotechnology , biochemistry , kinase , biophysics , biology , gene , organic chemistry
The dimeric regulatory subunits (R) of cAMP‐dependent protein kinase (PKA) are multidomain proteins with diverse functions. Other than inhibiting the catalytic subunit of PKA, one isoform (RIalpha) has been implicated in diseases. Though much is known about RIalpha, the role of the disulfide bond at the N‐terminus is poorly understood. Studies have shown that the cysteines involved in the disulfide bond contribute to its binding to A Kinase Anchoring Proteins (AKAPs) and may influence its localization to discrete sub‐cellular locations. One mutant of RIalpha, R74C, has been found in Carney complex patients. To date, the mechanism of action of the R74C mutation remains unknown. We determined if the disulfide bonding is altered in the R74C mutant and found a novel dimer. We are using mass spectrometry to analyze the disulfide bonding profile of this dimer. Additionally, studies are currently underway to see if there are changes in its binding to proteins, such as AKAPs, and whether there are changes in the sub‐cellular localization of this mutant.