Myristoylated alanine-rich C-kinase substrate (MARCKS)

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated, intrinsically disordered protein encoded by the MARCKS gene. It is a major cellular substrate for protein kinase C (PKC), with key roles in modulating the actin cytoskeleton, regulating cell shape, motility, secretion/exocytosis processes, phagocytosis, membrane trafficking, neural development/plasticity, and immune responses. MARCKS binds to actin filaments via its phosphorylation site domain when unphosphorylated but dissociates from both actin and membranes upon phosphorylation by PKC or binding to calcium-calmodulin. This dynamic localization acts as an "electrostatic switch" controlling its function between membrane-bound and cytoplasmic states. It sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in quiescent cells—a process reversed by PKC activation—thereby influencing exocytosis. MARCKS has been implicated in various physiological processes including embryonic development and inflammation; it also plays roles in disease contexts such as cancer progression/invasion and neuropsychiatric disorders

Other names

Protein kinase C substrate, 80 kDa proteinLight chain protein80K-LMACSPKCSL