High impact information on MGC137530

• MARCKS may be a regulated crossbridge between actin and the plasma membrane, and modulation of the actin crosslinking activity of the MARCKS protein by calmodulin and phosphorylation represents a potential convergence of the calcium-calmodulin and PKC signal transduction pathways in the regulation of the actin cytoskeleton [1].
• MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin [1].
• The myristoylated alanine-rich C kinase substrate (MARCKS) is a specific PKC substrate which has been implicated in macrophage activation, neuro-secretion and growth factor-dependent mitogenesis [2].
• The impaired membrane binding is associated with this mutant's inability to transduce several antitumorigenic signals as it fails to mediate phorbol ester-stimulated translocation of myristoylated alanine-rich protein kinase C substrate (MARCKS), to activate mitogen-activated protein kinase and to augment melatonin-stimulated neurite outgrowth [3].
• Here, we provide evidence for involvement of myristoylated alanine-rich protein kinase C substrate (MARCKS), a protein kinase C substrate, in chromaffin cell secretion [4].

Biological context of MGC137530

• Here we report that PKC-dependent phosphorylation displaces MARCKS from the membrane and that its subsequent dephosphorylation is accompanied by its reassociation with the membrane [2].
• The identity of the phosphorylation site domains from two proteins of overall 65% amino acid sequence identity suggests a potential role for this domain in the physiological function of the myristoylated alanine-rich C kinase substrate proteins [5].
• Myristoylated alanine-rich C kinase substrate (MARCKS), a major protein kinase C substrate, is an in vivo substrate of proline-directed protein kinase(s). A mass spectroscopic analysis of the post-translational modifications [6].
• Nucleotide sequence of a cDNA for the bovine myristoylated alanine-rich C kinase substrate (MARCKS) [7].
• ACAMP-81 is an acidic calmodulin binding protein with molecular mass of 81 kDa [8].

Anatomical context of MGC137530

• Myristoylation of MARCKS is required for effective binding to the plasma membrane where it colocalizes with PKC [2].
• Kinetics of interaction of the myristoylated alanine-rich C kinase substrate, membranes, and calmodulin [9].
• These results provide the first evidence for MARCKS involvement in chromaffin cell secretion and suggest that regulation of cortical F-actin cross-linking might be involved in this process [4].
• Demyristoylation of the major substrate of protein kinase C (MARCKS) by the cytoplasmic fraction of brain synaptosomes [10].
• The myristoylated alanine-rich C kinase substrate (MARCKS) is a major cellular substrate of protein kinase C. Its concentration in cells is important for the normal development of the central nervous system, and perhaps other physiological processes [11].

Associations of MGC137530 with chemical compounds

• It is heat-stable and copurifies with MARCKS during various steps (ammonium sulfate precipitation and gel filtration) [12].
• ACAMP-81 bound to the cysteine specific cleaved 51 kDa fragment derived from middle/tail region of synapsin I [8].
• Membrane binding of the myristoylated alanine-rich C kinase substrate (MARCKS) requires both its myristate chain and basic "effector" region [9].
• The effector domain of myristoylated alanine-rich C kinase substrate binds strongly to phosphatidylinositol 4,5-bisphosphate [13].
• In the complete protein kinase C assay mixture, two separate triple-labeling experiments demonstrated the colocalization of phosphatidylserine, protein kinase C, diacylglycerol, and the MARCKS peptide in domains [14].

Regulatory relationships of MGC137530

• Exposure of slices from a d 8 corpus luteum to prostaglandin F2alpha (PGF2alpha) during a 10-min incubation in the presence of [32P]-ortho-phosphate resulted in enhanced phosphorylation of MARCKS in membrane and cytosolic fractions compared to that of controls [15].

Other interactions of MGC137530

• Therefore, MARCKS, a major in vivo substrate of protein kinase C, is also an in vivo substrate of proline-directed protein kinase(s) such as mitogen-activated protein kinase or Cdk5 kinase [6].
• We report partial amino acid analysis of ACAMP-81 and its interaction with synapsin I [8].
• Myristoylated alanine-rich C kinase substrates (MARCKS) is a prominent protein kinase C (PKC) substrate that is targeted to the plasma membrane by an aminoterminal myristoyl group [16].
• Phosphorylation reverses the membrane association of peptides that correspond to the basic domains of MARCKS and neuromodulin [17].
• Since thrombin-induced MLC phosphorylation is also attenuated by these inhibitors, MARCKS may be involved in MLC kinase activation and subsequent BPAEC contraction [16].

Analytical, diagnostic and therapeutic context of MGC137530

• Molecular cloning, characterization, and expression of a cDNA encoding the "80- to 87-kDa" myristoylated alanine-rich C kinase substrate: a major cellular substrate for protein kinase C [18].
• MARCKS was also detected by immunoprecipitation [4].
• MARCKS was found in chromaffin cells by immunoblotting [4].
• Myristoylation mutant MARCKS-GFP (G2A) was observed solely in the cytoplasm, and no changes were detected in the intracellular location of this mutant MARCKS after treatment [19].
• Similarly, Western blot analysis of luteal proteins revealed that concentrations of MARCKS protein were greatest on d 8 and least on d 16 of the cycle (p < 0.01) [15].

References