How does myosin light chain kinase work?
Myosin light chain kinase (MLCK) plays a central role in regulating the actin-myosin interaction of smooth muscle. MLCK phosphorylates the light chain of myosin in the presence of Ca2+ and calmodulin (CaM) thereby activating myosin so that it can interact with actin.
Where is MLCK present?
Skeletal muscle MLCK is predominantly expressed in skeletal muscles but also detected in cardiac muscles6 although abundance of this MLCK in the heart may be controversial. Nevertheless, it was originally thought that skeletal muscle MLCK was involved in regulating cardiac MLC2 and thus cardiac phenotype.
What does myosin light chain phosphatase do?
Myosin light chain phosphatase (MLCP) is responsible for the dephosphorylation of the regulatory light chain (RLC) of the motor protein myosin-II, and so negatively regulates actomyosin-based contractility.
What happens when myosin light chain kinase is phosphorylated?
Myosin light chain kinase from smooth muscle has been shown to be phosphorylated by cyclic AMP-dependent protein kinase, which leads to a decrease in the affinity of the kinase for Ca2+ . calmodulin and, hence, a decrease in enzymatic activity.
Is MLCK inhibited by phosphorylation?
MLCK is phosphorylated by the Ca2+- and calmodulin-dependent protein kinase II (CaMKII); MLCP can be inhibited by phosphorylated CPI-17 and phosphorylation of MYPT by Rho kinase and arachidonic acid.
What activates myosin light kinase?
MLCK is activated by calmodulin in response to an increase in intracellular calcium. It then goes on to phosphorylate regulatory myosin light chains at residues serine 19 and threonine 18 [2][3]. These phosphorylations enhance the ATPase activity of actin-activated myosin and so promotes myosin-driven contraction.
Does PKA inhibit MLCK?
The prevailing concept is that phosphorylation of MLCK by PKA reduces the affinity of MLCK for Ca2+/CaM, when Ca2+/CaM is not bound to MLCK.
Is MLCK in skeletal muscle?
Western blot and quantitative-PCR showed that MLCK is expressed predominantly in fast-twitch skeletal muscle fibers with insignificant amounts in heart and smooth muscle.
What does MLCP do in smooth muscle?
Regulation of myosin light-chain phosphatase (MLCP) through regulation of myosin phosphatase target subunit 1 (MYPT1). (A) Active MLCP dephosphorylates the light chain of myosin (MLC20) at the Ser19 residue and induces smooth muscle relaxation.
How is myosin light chain phosphatase activated?
When the muscle needs to contract, calcium ions flow into the cytosol from the sarcoplasmic reticulum, where they activate calmodulin, which in turn activates myosin light-chain kinase (MLC kinase). When myosin phosphatase binds to myosin, it removes the phosphate group.
Does skeletal muscle have MLCK?
While the regulatory role of smooth muscle MLCK is well understood, the role of skeletal muscle MLCK in the regulation of contraction has not been fully characterized. However, MLCK hardly bound to myosin.
Where is the myosin light chain kinase located?
MYLK’s contain a catalytic core domain with an ATP binding domain. On either sides of the catalytic core sit calcium ion/calmodulin binding sites. Binding of calcium ion to this domain increases the affinity of MYLK binding to myosin light chain. This myosin binding domain is located at the C-Terminus end of the kinase.
Where does calcium ion bind to myosin light chain?
Binding of calcium ion to this domain increases the affinity of MYLK binding to myosin light chain. This myosin binding domain is located at the C-Terminus end of the kinase. On the other side of the kinase at the N-Terminus end, sits the actin-binding domain, which allows MYLK to form interactions with actin filaments, keeping it in place.
How does dephosphorylation of the myosin light chain occur?
Dephosphorylation of the myosin light chain (and subsequent termination of muscle contraction) occurs through activity of a second enzyme known as myosin light-chain phosphatase (MLCP). Protein kinase C and ROC Kinase are involved in regulating Calcium ion intake; these Calcium ions, in turn stimulate a MYLK, forcing a contraction.
What are the two classes of myosin light chains?
Myosin light chain classes. Structurally, myosin light chains belong to the EF-hand family, a large family of Ca 2+ – binding proteins. MLCs contain two Ca 2+ – binding EF-hand motifs. MLCs isoforms modulate the Ca 2+ of force transduction and cross-bridge kinetics. Myosin light chains (MLCs) can be broadly classified into two groups: