Myosin light chain phosphatase

Ribbon model of amino acids 1-299 of the regulatory subunit PPP1R12A of the MLCP in domestic fowl ( Gallus gallus ) according to PDB 1S70

The myosin light chain phosphatase (also MLCP or myosin light chain phosphatase ) is an enzyme which in the cells of the smooth musculature occurs. It dephosphorylates the regulatory light chain of myosin . This usually leads to smooth muscle relaxation . MLCP is a dimer of the catalytic subunit PPP1CB ( EC  3.1.3.53 ) and the regulatory subunit (one of PPP1R12A / B / C) that determines the substrate. Binding of PPP1CB to other subunits leads to different substrate specificities.

MLCP has an antagonistic effect on the enzyme myosin light chain kinase .

The catalyzed reaction is:

[Myosin light chain] phosphate + H ₂ O [myosin light chain] + PP _i ${\displaystyle \longrightarrow }$

Mechanism of action

The relaxing signal cascades with the second messenger cAMP or cGMP increase the activity of protein kinase A (PKA) and protein kinase G (PKG). This in turn leads to an increased activity of myosin light chain phosphatase.

In its effect, it splits a phosphate from the light chain of the myosin, which lowers the calcium sensitivity of the myofilaments. Higher Ca ²⁺ concentrations are now necessary to trigger a contraction. In total, the relative proportion of relaxed muscle cells in the smooth muscle increases.

It is not yet known exactly by which mechanism the PKA and PKG increase the activity of the MLCP. An interaction with the Rho / Rho kinase pathway is suspected.

Regulation together with myosin light chain kinase

The phosphorylation of myosin is also regulated by myosin light chain kinase MLCK . The two enzymes MLCK and MLCP with an antagonistic effect keep the muscle in a certain phosphorylation and tension ratio.

A high activity of the MLCK means a contraction and a high activity of the MLCP means a relaxation of the smooth muscle z. B. on vessels and bronchi. That is why the activities of the MLCK and the MLCP are neurohumorally regulated in a variety of ways via the vegetative nervous system, whereby the pathways always antagonistically activate one enzyme and inhibit the other. Examples:

• α ₁ -adrenoreceptor : (Gq-coupled) [IP ₃ ] ↑, [Ca ²⁺ ] ↑, [Ca ²⁺ - calmodulin complex] ↑, MLCK activity ↑
• α ₁ adrenoreceptor : (Gq-coupled) [DAG] ↑, PKC activity ↑, MLCP activity ↓
• β ₂ adrenoreceptor : (Gs-coupled) [cAMP] ↑, PKA activity ↑, MLCK activity ↓
• β ₂ adrenergic receptor : (Gs-coupled) [cAMP] ↑, PKA activity ↑, MLCP activity ↑
• Guanylate cyclase (soluble): (by binding of NO ) [cGMP] ↑, PKG activity ↑, MLCP activity ↑

Individual evidence

1. ↑ ^{a b} Robert F. Schmidt (editor), Florian Lang (editor), Manfred Heckmann (editor): Physiologie des Menschen . Springer Berlin Heidelberg; Edition: 31st, revised. u. actual Edition (October 4, 2010).
2. ↑ ^{a b c d e} Joachim Rassow , Rainer Deutzmann, Roland Netzker, Karin Hauser: Dual Series Biochemistry . 2nd edition, current 2008.