The C2-like domain contributed to the multimeric conformation of the E protein. The domain facilitated E's translocation to the phospholipid membrane on the cell surface. However, the C2-like domain of the E protein activated the PKC pathway as well. Protein kinase C (PKC) isoforms are expressed in varying quantities in various vascular beds' smooth muscle (VSM) . The primary regulator of vascular smooth muscle (VSM) function is protein kinase C (PKC) . VSM is critical for maintaining vascular tone . Protein kinase C is first implicated in smooth muscle contraction control. Phorbol ester has been shown to generate a slow-developing persistent contraction. PKC that has been inactivated is primarily cytoplasmic. After activation, it undergoes phosphorylation, maturation, and translocation to the surface membrane, nucleus, endoplasmic reticulum, and other organelles . Protein kinase C's long-term association with the membrane may render it proteolytic. The produce is protein kinase M, released into the cytoplasm, phosphorylating and relaxing myosin . PKC inhibitors effectively decrease vasoconstriction generated by agonists. PKC initiates a cascade of phosphorylation processes . It phosphorylates calmodulin directly and activates mitogen-activated protein kinase and filament-related proteins. The phosphorylation will reduce these filament proteins' inhibitory effect on the rate of cross-bridge circulation. Due to the sluggish creation of force, it results in a slower cross-bridge circulation . Thus, phosphorylation of MLCK by PKC may result in vascular relaxation . It may the a significant contributor to vascular leakage.