EMD - Calbiochem - Inhibitors: Phosphorylation/Dephosphorylation - Protein Kinase A (PKA; cAMP-Dependent Protein Kinase)

		Technical Resources

		Technical Information

		Calbiochem Information

		Inhibitor Resource

		Phosphorylation Dephosphorylation

		AKT
		AMPK
		Aurora Kinase
		Cam Kinase
		Casein Kinase
		Checkpoint Kinase
		Cyclin-dependent Kinase
		DNA-Dependent Protein Kinase
		Glycogen Synthase Kinase
		c-Jun N-Terminal Kinase
		IP3 Kinase & TGF-b Receptor I Kinase
		MAP Kinase
		MLCK
		PI 3 Kinase
		Protein Kinase A
		Protein Kinase C
		Protein Kinase G
		Protein Phosphatase
		Protein Tyrosine Kinase
		Raf Kinase
		Rho Kinase
		Sphingosine Kinase

Phosphorylation/Dephosphorylation: PKA; cAMP-Dependent Protein Kinase

Inhibitors I Table 1: Selected Protein Kinase Inhibitors

The cAMP-dependent protein kinase (protein kinase A; PKA) pathway is one of the most versatile signaling pathways in eukaryotic cells. Various extracellular signals converge on this signaling pathway through ligand binding to G protein-coupled receptors. Hence, the PKA pathway is tightly regulated at several levels to maintain specificity in the multitude of signal inputs. PKA is composed of two regulatory and two catalytic subunits. In the holoenzyme, the regulatory subunits are bound to the active site of the catalytic subunits, inactivating them. Binding of cAMP to the regulatory subunits causes a conformational change that releases and activates the two catalytic subunits. The active catalytic subunits can then phosphorylate serine and/or threonine residues on the substrates in the cytosol and in the nucleus. When the levels of cAMP begin to fall, the regulatory subunits regain their affinity towards the catalytic subunits and form the inactive holoenzyme. If cAMP levels remain persistently elevated, many cells change their behavior and may either differentiate, proliferate, or undergo apoptosis.

PKA holoenzyme exists in two forms, type I and type II. They contain identical catalytic subunits; however, their regulatory subunits differ (RI or RII dimer). Type I holoenzyme is predominantly cytosolic, whereas type II holoenzyme is compartmentalized to subcellular organelles via specific anchoring proteins. The turnover rate of free type I regulatory subunit is significantly higher than that of type II subunits. When free catalytic subunit is microinjected into the cytoplasm of intact cells, it migrates to the nucleus, whereas the free regulatory subunit remains only in the cytoplasm following microinjection. When both subunits are co-injected, the regulatory subunit blocks the nuclear migration of the catalytic subunit. CREB is a major nuclear target for the catalytic subunit that binds to cAMP response elements (CREs) in the promoter regions of cAMP-responsive genes. Phosphorylation of CREB proteins alters their ability to form dimers and to interact with CREs.

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Table 1: Selected Protein Kinase Inhibitors

Product	Cat. No.	CKI	CKII	MLCK	PKA	PKC	PKG
A3, Hydrochloride	100122	80	5.1	7.4	4.3	47.0	3.8
Adenosine 3',5'-cyclic Monophosphorothioate, Rp-Isomer, Triethylammonium Salt	116814	-	-	-	11.0	-	-
Adenosine 3',5'-cyclic Monophophorothioate, 8-Bromo-2'-Monobutyryl-, Rp-Isomer, Sodium Salt	116813
Adenosine 3',5'-cyclic Monophophorothioate, 8-Chloro-, Rp-Isomer, Sodium Salt Analog of Cat. No. 116814.	116819	-	-	-	50 (type I PKA)	-	-

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Inhibitors: Protein Kinase A (PKA; cAMP-Dependent Protein Kinase)

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