Figure 4.

The regulation of ADF/cofilins through kinase and other pathways. In many cell types, the LIM kinases regulate ADF/cofilin activity by phosphorylation. LIM kinases are themselves activated by a host of upstream kinases including the Rho-activated kinase ROCK, Ca²⁺ and phospholipid-dependent kinase protein kinase C and Rac-activated kinase PAK1, which are in turn activated by small G proteins or diacyglycerol (DAG). Phosphorylated ADF/cofilins do not bind actin. Perhaps counterintuitively, the severing and depolymerization of actin filaments by ADF/cofilins is activated by phosphorylation, as this leads to dissociation of ADF/cofilin from actin, leaving it free to sever and depolymerize actin once more after it is dephosphorylated by phosphatase activity. Depolymerization would be increased further if ADF/cofilin phosphatase activity as well as LIM kinase activity were increased.