Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The myristoylated, alanine-rich C kinase (PKC) substrate (MARCKS) is a major, specific substrate of PKC that is phosphorylated during macrophage and neutrophil activation, growth factor-dependent mitogenesis and neurosecretion. MARCKS is also a calmodulin-binding protein and binding of calmodulin inhibits phosphorylation of the protein by PKC. Several recent observations from our laboratories suggest a role for MARCKS in cellular morphology and motility. First, in macrophages MARCKS is located at points of cellular adherence where actin filaments insert at the plasma membrane and is released to the cytoplasm upon activation of PKC. Second, during neutrophil chemotaxis MARCKS undergoes a cycle of release from, and reassociation with, the plasma membrane. Third, in vitro, MARCKS is an F-actin cross-linking protein whose activity is inhibited by PKC-mediated phosphorylation and by binding to calmodulin. MARCKS therefore appears to be a regulated cross-bridge between actin and the plasma membrane. Regulation of the plasma membrane-binding and actin-binding properties of MARCKS represents a convergence of the PKC and calmodulin signal transduction pathways in the control of actin cytoskeleton-plasma membrane interactions.
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PMID:Calmodulin and protein kinase C cross-talk: the MARCKS protein is an actin filament and plasma membrane cross-linking protein regulated by protein kinase C phosphorylation and by calmodulin. 139 31

Ischemia is the central pathogenic factor underlying a spectrum of intestinal disorders. The study of the cellular signaling responses to ischemic stress in nonepithelial cells has progressed substantially in the previous several years, but little is known about the response in epithelial cells. Unique features of the epithelial response to ischemic stress suggest differential regulation with regards to signaling. The PKC family of proteins has been implicated in ischemic stress in nonepithelial systems. The role of PKC isoforms in chemical ischemia in intestinal epithelial cells is evaluated in this study. Additionally, the phosphorylation of the F-actin cross-linking protein myristoylated alanine-rich C kinase substrate (MARCKS) is also studied. Chemical ischemia resulted in the transient activation of only the isoform PKC-epsilon as detected by translocation employing the subcellular fractionation technique. The pharmacological agonists phorbol 12-myristate 13-acetate and carbachol also led to the translocation of PKC-epsilon. By immunofluoresence, MARCKS is noted to be located at the lateral membrane under control conditions. In response to carbachol, MARCKS translocates to the cytosol, indicating its phosphorylation, which is additionally confirmed biochemically. Consistent with this observation, carbachol induces the translocation of PKC-epsilon to proximity with MARCKS at the lateral membrane. In response to chemical ischemia, MARCKS fails to translocate and phosphorylation does not increase. Additionally, the translocation of PKC-epsilon is not to the lateral membrane but rather basally. The data suggest that the differential translocation of PKC-epsilon in response to pharmacological agonists versus ischemic stress may lead to different effects on downstream targets.
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PMID:Differential subcellular targeting of PKC-epsilon in response to pharmacological or ischemic stimuli in intestinal epithelia. 1535 94

Macrophage phagocytosis plays an important role in host defense. The molecular mechanism, especially factors regulating the phagocytosis, however, is not completely understood. In the present study, we found that response gene to complement 32 (RGC-32) is an important regulator of phagocytosis. Although RGC-32 is induced and abundantly expressed in macrophage during monocyte-macrophage differentiation, RGC-32 appears not to be important for this process because RGC-32-deficient bone marrow progenitor can normally differentiate to macrophage. However, both peritoneal macrophages and bone marrow-derived macrophages with RGC-32 deficiency exhibit significant defects in phagocytosis, whereas RGC-32-overexpressed macrophages show increased phagocytosis. Mechanistically, RGC-32 is recruited to macrophage membrane where it promotes F-actin assembly and the formation of phagocytic cups. RGC-32 knock-out impairs F-actin assembly. RGC-32 appears to interact with PKC to regulate PKC-induced phosphorylation of F-actin cross-linking protein myristoylated alanine-rich protein kinase C substrate. Taken together, our results demonstrate for the first time that RGC-32 is a novel membrane regulator for macrophage phagocytosis.
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PMID:Response gene to complement 32 protein promotes macrophage phagocytosis via activation of protein kinase C pathway. 2497 10