The MARCKS family of phospholipid binding proteins: regulation of phospholipase D and other cellular components.
Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP) are essential proteins that are implicated in coordination of membrane-cytoskeletal signalling events, such as cell adhesion, migration, secretion, and phagocytosis in a variety of cell types. The most prominent structural feature of MARCKS and MRP is a central basic effector domain (ED) that binds F-actin, Ca2+-calmodulin, and acidic phospholipids; phosphorylation of key serine residues within the ED by protein kinase C (PKC) prevents the above interactions. While the precise roles of MARCKS and MRP have not been established, recent attention has focussed on the high affinity of the MARCKS ED for phosphatidylinositol 4,5-bisphosphate (PIP2), and a model has emerged in which calmodulin- or PKC-mediated regulation of these proteins at specific membrane sites could in turn control spatial availability of PIP2. The present review summarizes recent progress in this area and discusses how the above model might explain a role for MARCKS and MRP in activation of phospholipase D and other PIP2-dependent cellular processes.
Sundaram
Meenakshi
M
Atlantic Research Centre, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
Cook
Harold W
HW
Byers
David M
DM
D002148:Calmodulin-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins; D008954:Models, Biological; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011487:Protein Conformation; D011493:Protein Kinase C / Q000378:metabolism
D002148:Calmodulin-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins; C000619710:MARCKS protein, human; C070177:MARCKSL1 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010743:Phospholipids; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C; D010739:Phospholipase D