PKA

108068-98-0
KT 5720
108068-98-0
H-7 dihydrochloride
108930-17-2
1135306-29-4
H-9 dihydrochloride
116700-36-8
121932-06-7
CCG215022
1813527-81-9
201422-03-9
Kemptide
65189-71-1
PKI (5-24)
99534-03-9

Background


An overview of PKA

PKA is a tetramer containing regulatory subunits and catalytic subunits with four regulatory subtypes (RIα, RIβ, RIIα, RIIβ) and three catalytic subtypes (Cα, Cβ, Cγ). PKA belongs to the serine/threonine protein kinase. In the AC-cAMP-PKACREB pathway, adenylate cyclase (AC) catalyzes the production of cyclic adenosine monophosphate (cAMP) by intracellular ATP. As an intracellular signaling substance, cAMP is mainly activated by PKA to realize signal transduction. Its functions involve many aspects including the plasticity of synapse, exocytosis and gene transcription. PKA is expressed throughout the brain, especially in the cerebral cortex, thalamus, and amygdala. Moreover, it is moderately expressed in the midbrain, nucleus accumbens, and ventral tegmental areas.

Targeted drugs for PKA

PKA plays an important regulatory role in the changes in neuronal excitability caused by acute or chronic noxious stimulation. The PKA antagonist h-89 can relieve neuropathic and inflammatory pain in rats to different degrees. PKA can promote drug-induced synaptic plasticity. Moreover, PKA promotes the transport of AMPA receptors to the cell membrane by phosphorylating the GluR1 subunit of the AMPA receptor. Both dopamine D1 receptor agonists SKF81297 and SCH23390 and the PKA activator Sp-cAMPS increased the expression of GluR1 cells on the rat nucleus accumbens. Increased glutamate levels in the nucleus accumbens of morphine-dependent withdrawal rats may be due to some selective inhibitors of PKA1 caused by the release of glutamate by the corresponding synapses. These inhibitors include 8-C1-cAMP and mixed backbone DNA/RNA antisense oligonucleotides (MBOAS-PKA1). They have anti-cancer effects and can inhibit growth factors and angiogenic factors.

PKA and diseases

A series of agonists and antagonists targeting various types of prostanoid receptors have received increasing attention, such as DP2 antagonists and allergies, EP4 and bone resorption, EP1 and EP3 antagonists and tumorigenesis. It is promising to synthesize PG analogues that are superior to the parent, and to find the ideal anti-asthmatic drug, anti-gastrointestinal ulcer drug, cardiovascular disease and fertility control.

References:

Taylor, S. S., Zhang, P., Steichen, J. M., Keshwani, M. M., & Kornev, A. P. (2013). Pka: lessons learned after twenty years ☆. Biochimica Et Biophysica Acta Proteins & Proteomics, 1834(7), 1271-1278.

Liu, S., Shapiro, J. M., Saloustros, E., & Stratakis, C. A. (2016). Bone abnormalities in mice with protein kinase a (pka) defects reveal a role of cyclic amp signaling in bone stromal cell-dependent tumor development. Hormone & Metabolic Research, 48(11), 714-725.