MacMARCKS, a novel member of the MARCKS family of protein kinase C substrates.
MARCKS is a specific protein kinase C (PKC) substrate that binds both calmodulin and actin and is phosphorylated during phagocyte activation, neurosecretion, and growth factor-dependent mitogenesis. We report here on MacMARCKS, a MARCKS homolog, whose synthesis is dramatically increased in macrophages when these cells are exposed to bacterial lipopolysaccharide. We have purified rabbit MacMARCKS and cloned its cDNA from rabbit and mouse. The effector domains of MacMARCKS and MARCKS are nearly identical, and both proteins bind calmodulin in a phosphorylation-regulated manner. MacMARCKS and MARCKS also share a second, highly conserved region also found in the internalization domain of the mannose-6-phosphate receptor. Our data suggest the existence of a family of PKC substrates that are targeted to different subcellular locations and that function to integrate PKC and calcium/calmodulin-dependent signals in the control of the plastic actin cytoskeleton.
Li
J
J
Rockefeller University, New York, New York 10021.
Aderem
A
A
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification; D011817:Rabbits; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D000199:Actins; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C000619711:Marcks protein, mouse; C512945:Marcksl1 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C