PKAdependent

PKAdependent describes cellular processes that require protein kinase A (PKA) activity. PKA is a cAMP-dependent serine/threonine kinase that regulates a wide range of cellular functions by phosphorylating target proteins on serine or threonine residues. In most signaling contexts, extracellular signals activate Gs-coupled receptors, stimulating adenylyl cyclase to raise intracellular cAMP, which binds the regulatory subunits of the PKA holoenzyme and releases the active catalytic subunits.

PKA exists as type I and type II holoenzymes, each composed of two regulatory and two catalytic subunits. Different regulatory subunits confer distinct localization and regulation, a specificity often achieved through A-kinase anchoring proteins (AKAPs) that tether PKA to particular substrates or cellular compartments. This spatial organization enables precise control of phosphorylation events and minimizes cross-talk with other kinases.

PKA-dependent phosphorylation affects a broad spectrum of substrates. It modulates transcription by phosphorylating CREB, leading to changes in gene expression. It also regulates metabolic enzymes (for example, glycogen phosphorylase kinase), ion channels, transporters, and cytoskeletal components. The resulting effects span glucose homeostasis, memory formation, cardiac contractility, and neuronal signaling, among others. PKA can have fast non-transcriptional effects as well as longer-term transcriptional programs.

Regulation of PKA activity involves not only cAMP levels but also phosphatases that counteract phosphorylation and various inhibitors. Experimental approaches to study PKA-dependence include the use of cAMP analogs, PKA inhibitors, and AKAP-disrupting tools to dissect localization-dependent effects. In summary, PKA-dependent pathways are those in which PKA activity is essential for the observed cellular outcome.