Activation of Protein Kinase C‐α and Translocation of the Myristoylated Alanine‐Rich C‐Kinase Substrate Correlate with Phorbol Ester‐Enhanced Noradrenaline Release from SH‐SY5Y Human Neuroblastoma Cells

Goodall, Anna R.; Turner, Neil A.; Walker, John H.; Ball, Stephen G.; Vaughan, Peter F. T.

doi:10.1046/j.1471-4159.1997.68010392.x

Cited by 49 publications

(27 citation statements)

References 24 publications

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“…When phosphorylated by activated PKC, MARCKS translocates from the plasma membrane to the cytoplasm. 24,25 Adler and co-workers showed that MARCKS is required for mucus secretion by human bronchial epithelial cells in culture. 26 MARCKSrelated peptide can therapeutically reduce mucus secretion in the airways of human patients with asthma, chronic bronchitis, and cystic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA 429 Regulates Mucin Gene Expression and Secretion in Murine Model of Colitis

Alam

Kim

et al. 2016

ECCOJC

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Background and Aims: miRNAs are non-coding RNAs that play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. We aimed to detect miRNAs related to ulcerative colitis [UC], identify their target molecules, and analyse the correlation between the miRNAs and their target genes in colorectal cells and dextran sulphate sodium [DSS]-induced mouse colitis. Methods: UC-associated miRNAs were identified by miRNA microarray analysis using DSS-induced colitis and normal colon tissues. The results were validated by quantitative real-time polymerase chain reaction [RT-PCR]. We identified target genes of MIR429, a colitis-associated miRNA, from our screen by comparing the mRNA microarray analysis in MIR429-overexpressed cells with predicted candidate target genes. We constructed luciferase reporter plasmids to confirm the effect of MIR429 on target gene expression. The protein expression of the target genes was measured by western blot,enzyme-linked immunosorbent assay [ELISA] analysis, or immunohistochemistry. Results: We identified 37 DSS-induced colitis associated miRNAs. We investigated MIR429 that is down-regulated in DSS-induced colitis, and identified 41 target genes of MIR429. We show that the myristoylated alanine-rich protein kinase C substrate [MARCKS] is a direct target of MIR429. MARCKS mRNA and protein expression levels are down-regulated by MIR429, and MIR429 regulates the expression of MARCKS and MARCKS-mediated mucin secretion in colorectal cells and DSS-induced colitis. In addition, anti-MIR429 up-regulates MARCKS expression in colorectal cell lines. Conclusion: Our findings suggest that MIR429 modulates mucin secretion in human colorectal cells and mouse colitis tissues by up-regulating of MARCKS expression, thereby making MIR429 a candidate for anti-colitis therapy in human UC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA 429 Regulates Mucin Gene Expression and Secretion in Murine Model of Colitis

Alam

Kim

et al. 2016

ECCOJC

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“…MARCKS has been implicated in processes requiring signal-dependent changes in actin-membrane plasticity and cytoskeletal restructuring. 80,81 It can crosslink actin, bind calcium/ calmodulin, interact with the plasma membrane, and has been linked to organization of polyphosphoinositide (PI (4,5)P 2 ) signaling domains, 82,83 regulation of phospholipase D, 84 secretion, 85,86 and phagocytosis. 87 MARCKS is preferentially expressed in dendritic branches and axon terminals within limbic and limbic-associated regions of brain, as well as neuronal growth cones necessary for normal brain development.…”

Section: Lithium and Marcks: A Downstream Target For Pi/pkc Signalingmentioning

confidence: 99%

Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks

2003

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The clinical efficacy of lithium in the prophylaxis of recurrent affective episodes in bipolar disorder is characterized by a lag in onset and remains for weeks to months after discontinuation. Thus, the long-term therapeutic effect of lithium likely requires reprogramming of gene expression. Protein kinase C and glycogen synthase kinase-3 signal transduction pathways are perturbed by chronic lithium at therapeutically relevant concentrations and have been implicated in modulating synaptic function in nerve terminals. These signaling pathways offer an opportunity to model critical signals for altering gene expression programs that underlie adaptive responses of neurons to long-term lithium exposure. While the precise physiological events critical for the clinical efficacy of lithium remain unknown, we propose that linking lithium-responsive genes as a regulatory network will provide a strategy to identify signature gene expression patterns that distinguish between therapeutic and nontherapeutic actions of lithium.

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“…When phosphorylated by activated protein kinase C (PKC), MARCKS translocates from the plasma membrane to the cytoplasm (4,5). In previous studies in airway secretory cells, we demonstrated that MARCKS, upon phosphorylation, translocates to the cytoplasm, and there binds to membranes of intracellular mucin granules (2,3).…”

mentioning

confidence: 97%

MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro

Park

Fang

Crews

et al. 2008

Am J Respir Cell Mol Biol

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We have reported previously that myristoylated alanine-rich C kinase substrate (MARCKS) is a key regulatory molecule controlling mucin secretion by airway epithelial cells in vitro and in vivo. The results of those studies supported a mechanism whereby MARCKS, upon phosphorylation by protein kinase C (PKC), translocates from plasma membrane to cytoplasm, where its binding to membranes of intracellular mucin granules is a key component of the secretory pathway. It remains unknown how MARCKS is targeted to and/or preferentially attaches to mucin granule membranes. We hypothesized that the chaperone cysteine string protein (CSP) may play an important role in this process. CSP was shown to associate with membranes of intracellular mucin granules in well-differentiated normal human bronchial epithelial (NHBE) cells in vitro, as determined by ultrastructural immunohistochemistry and Western blotting of isolated granule membranes. CSP in these cells complexed with MARCKS, as shown by co-immunoprecipitation. Given reported associations between CSP and a second chaperone, heat shock protein 70 (HSP70), a role for HSP70 in the MARCKS-dependent secretory mechanism also was investigated. HSP70 appeared to form a trimeric complex with MARCKS and CSP associated with mucin granule membranes within airway epithelial cells. Transfection of the HBE1 human bronchial epithelial cell line with siRNAs targeting sequences of MARCKS, CSP, or HSP70 resulted, in each case, in significant knockdown of expression of these proteins and subsequent attenuation of mucin secretion. The results provide the first evidence that CSP and HSP70, and their interactions with MARCKS, are involved in mucin secretion.

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Activation of Protein Kinase C‐α and Translocation of the Myristoylated Alanine‐Rich C‐Kinase Substrate Correlate with Phorbol Ester‐Enhanced Noradrenaline Release from SH‐SY5Y Human Neuroblastoma Cells

Cited by 49 publications

References 24 publications

MicroRNA 429 Regulates Mucin Gene Expression and Secretion in Murine Model of Colitis

MicroRNA 429 Regulates Mucin Gene Expression and Secretion in Murine Model of Colitis

Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks

MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro

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