Merck UK - Calbiochem - Inhibitors: Phosphorylation/Dephosphorylation

		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: Myosin Light Chain Kinase (MLCK) Inhibitors

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Table 1: Selected PK Inhibitors I MLCK Inhibitors

Myosin light chain kinase (MLCK), a Ca²⁺-calmodulin dependent multi-functional enzyme, plays a critical role in the regulation of smooth muscle contraction and cellular migration. It regulates the contractile interaction between actin microfilaments and conventional smooth muscle and non-muscle myosin II. MLCK is composed of an N-terminal actin-binding domain, a central kinase domain, and a C-terminal myosin-binding domain. The kinase domain activates the interaction of smooth-muscle myosin with actin by phosphorylating the myosin light chain. MLCK phosphorylates a specific site on the N-terminus of the regulatory light chain of myosin II. This phosphorylation is responsible for coupling increased Ca²⁺ concentration with smooth muscle contraction.

In the presence of Ca²⁺, the C-terminal domain of calmodulin binds to the N-terminus of the calmodulin-binding sequence of MLCK followed by the binding of the N-terminal domain to the C-terminus of the calmodulin-binding sequence. MLCK is reported to bind the actin filament in a manner that also allows the simultaneous binding of the other major thin filament components; calponin, tropomyosin, etc. The binding site is suggested to be on the outside of sub-domain 1. There is approximately one MLCK molecule for every 100 actin molecules in smooth muscle and each MLCK contains at least three of the DFRXXL motifs allowing each molecule to bind three actins (K_d= 4 mM).

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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: Myosin Light Chain Kinase (MLCK)

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