<unk>  have two related functions in the C-terminal myosin-binding domain of smooth muscle myosin light chain kinase (MLCK). First,<unk>  stabilizes myosin filaments in the presence of ATP. Second,<unk>  can modulate the level of myosin light chain phosphorylation. In this latter role, multiple mechanisms have been suggested. One hypothesis is that light chain phosphorylation is diminished by the direct competition of KRP and MLCK for myosin, resulting in a loss of contraction.<unk>  also inhibits the phosphorylation of myosin filaments while having no effect on phosphorylation of the isolated smooth-muscle myosin regulatory light chain (ReLC). However, when<unk>  was phosphorylated by MLCK, the<unk> -induced inhibition of myosin phosphorylation was removed, which indicates the existence of a<unk> -dependent modulatory pathway in smooth-muscle regulation. In this part we must say that the phosphorylation of<unk>  can be enhanced by the concentration of Ca2+ and calmodulin. Kinase-related protein<unk>  binds to dephosphorylated smooth myosin near the junction between the rod and the catalytic head region (S-I). This interaction is prevented by MLCK-catalysed phosphorylation of myosin and conversely, the rate of myosin phosphorylation is in turn inhibited by KRP in vitro. As a consequence of this, in vivo KRP might slow down the rate of myosin phosphorylation by myosin light chain kinase (MLCK) and, therefore, tension development. When the intracellular Ca2+ level is decreasing, the KRP can also accelerate muscle relaxation by lowering the ratio of phosphorylated to phosphorylated myosin. KRP is also an important structural regulator of myosin filaments. Smooth muscle myosin, under physiological conditions in vitro, can adapt two relatively and different stable conformations. When the myosin is in the extended conformation, it is active and able to combine with other myosin molecules to form thick filaments which are fundamental for effective contraction. Upon ATP binding, the rod part of unphosphorylated myosin molecule folds into thirds, so that the head –rod junction is brought close to the middle of the rod and stabilized there, presumable by interacting with both the 20 KDa light chains and the neck region. This interaction is prevented by the MLCK-dependent light chain phosphorylation, resulting in the unfolding of myosin monomers and their rapid polymerization into filaments. The binding of KRP to the neck region folded, ATP-bound dephosphorylated myosin also promotes unfolding and filament formation, thus looking like light chain phosphorylation. This could be a physiologically significant phenomenon considering the high concentration of ATP always present in smooth muscle cells. Thus, Kinase-related protein may have a very important role in relaxed smooth muscle by keeping dephosphorylated myosin in the filamentous state ready for the next rapid contractile response. Experiments aimed at testing this hypothesis indicated that under appropriate conditions a small excess of KRP is enough to form an equimolar complex with smooth muscle myosin and to cause its complete polymerization in the presence of ATP. Experiments where it has been tested this hypothesis, indicated that in appropriated conditions, a small excess of KRP is enough to form an equimolar complex with smooth muscle myosin and in the presence of ATP, cause its complete polymerization.
Telokin
Equilin
Reelin
Clathrin
Progerin
Retapamulin
Eribulin
Collectin