Crystallographic, kinetic, and calorimetric investigation of PKA interactions with L-type calcium channels and Rad GTPase.

ABSTRACT: β-Adrenergic signaling activates cAMP-dependent PKA, which regulates the activity of L-type voltage-gated calcium channels such as Ca_V1.2. Several PKA target sites in the C-terminal tail of Ca_V1.2 have been identified, and their phosphorylation has been suggested to increase currents in specific tissues or heterologous expression systems. However, augmentation of Ca_V1.2 currents in the heart is instead mediated by phosphorylation of Rad, a small GTPase that can inhibit Ca_V1.2. It is unclear how each of the proposed target sites in Ca_V1.2 and Rad rank toward their recognition by PKA, which could reveal a preferential phosphorylation. Here, we used quantitative assays on three Ca_V1.2 and four Rad sites. Isothermal titration ca

SUBMITTER: Yoo R 

PROVIDER: S-EPMC11728977 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature