Protein kinase A catalytic subunit isoform PRKACA; History, function and physiology

Abstract

Our appreciation of the scope and influence of second messenger signaling has its origins in pioneering work on the cAMP-dependent protein kinase. Also called protein kinase A (PKA), this holoenzyme exists as a tetramer comprised of a regulatory (R) subunit dimer and two catalytic (C) subunits. Upon binding of two molecules of the second messenger cAMP to each R subunit, a conformational change in the PKA holoenzyme occurs to release the C subunits. These active kinases phosphorylate downstream targets to propagate cAMP responsive cell signaling events. This article focuses on the discovery, structure, cellular location and physiological effects of the catalytic subunit alpha of protein kinase A (encoded by the gene PRKACA). We also explore the potential role of this essential gene as a molecular mediator of certain disease states.

Exosomes derived from embryonal and alveolar rhabdomyosarcoma carry differential miRNA cargo and promote invasion of recipient fibroblasts

“…Significantly represented networks featured proteins previously implicated in ARMS biology (GSK3b, MDM2, CDKN1A, CDKN2A, IGF1R)4344454647, proteins involved in immune evasion and tumor metastasis (CXCL8, CSF1, IFNAR1, CCR2, CASR)4849505152, stemness (SOX2, POU5F1)5354, tumor cell proliferation and invasion (YBX1)41, or have been associated with other tumor types with a possible role in tumor biology (PRKACA, MYO1C, BRINP3)555657. The finding of the miRNA networks targeting proteins involved in stemness, immune evasion and metastasis, enriched in ARMS but not ERMS exosomes, suggests that paracrine signaling via exosomes may have differential effects on mediating the known aggressive behavior of ARMS.…”

Expression of protein kinase A regulatory subunits in benign and malignant human thyroid tissues: A systematic review

“…(29). In addition, circulating PRKACA has been detected in the sera of patients affected by carcinomas of the colon, kidney, rectum, prostate, lung, adrenal gland, as well as those with lymphomas (30)(31)(32).…”

Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation to Preferentially Phosphorylate Membrane Substrates

“…Several studies have suggested that PKA-C may exhibit kinase activity without leaving PKA-R (Johnson et al, 1993; Smith et al, 2013; Yang et al, 1995). However, the vast majority of the literature indicates that PKA-C is released from the AKAP/PKA-R complex during physiological elevations of cAMP concentration (Beavo et al, 1974a; Buxton and Brunton, 1983; Francis and Corbin, 1994; Johnson et al, 2001; Turnham and Scott, 2016). Liberated PKA-C is generally viewed as a cytosolic protein because of its high solubility (Johnson et al, 2001).…”