Protein kinase D2 regulates chromogranin A secretion in human BON neuroendocrine tumour cells

Wichert, Götz von; Edenfeld, Teresa; Adler, Gail K.; Seufferlein, Thomas

doi:10.1200/jco.2008.26.15_suppl.22165

Cited by 7 publications

(12 citation statements)

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“…CgA secretion is consistent with previous studies that had demonstrated that this protein is secreted by all three cell lines (11,(17)(18)(19)(20). Chromogranin A was used as the positive controls for the analysis of each preparation and each cell line during this investigation.…”

Section: Identification Of CM Proteins Using Sds-page and Mass Spectrsupporting

confidence: 87%

Identification of Mac-2-binding Protein as a Putative Marker of Neuroendocrine Tumors from the Analysis of Cell Line Secretomes

Srirajaskanthan

Caplin

Waugh

et al. 2010

Molecular & Cellular Proteomics

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Section: Identification Of CM Proteins Using Sds-page and Mass Spectrsupporting

confidence: 87%

Identification of Mac-2-binding Protein as a Putative Marker of Neuroendocrine Tumors from the Analysis of Cell Line Secretomes

Srirajaskanthan

Caplin

Waugh

et al. 2010

Molecular & Cellular Proteomics

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“…A report indicating that nearly all tissues in PKD2-deficient or PKD3-defective mice develop and function normally (6) argues against an essential requirement for PKD2-PKD3 heterodimers in broadly regulating TGN fission or F-actin-based motility in vivo. Only PKD2 was required for constitutive and regulated production of TGN-derived vesicles that mediate chromogranin A secretion from BON endocrine cells (11). PKD1 or PKD3, presumably acting as monomers or homo-oligomers, can independently regulate phosphorylation and nucleus to cytoplasm translocation of HDAC7 in B cells (22).…”

Section: Discussionmentioning

confidence: 99%

“…In BON neuroendocrine cells, vesicle biogenesis at the TGN and chromogranin A secretion were regulated solely by PKD2 (11). PKD1 or PKD3 depletion had no effect.…”

mentioning

confidence: 90%

A Novel Conserved Domain Mediates Dimerization of Protein Kinase D (PKD) Isoforms

Aicart-Ramos

Land

et al. 2016

Journal of Biological Chemistry

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Edited by Alex TokerProtein kinase D (PKD) isoforms are protein kinase C effectors in signaling pathways regulated by diacylglycerol. Important physiological processes (including secretion, immune responses, motility, and transcription) are placed under diacylglycerol control by the distinctive substrate specificity and subcellular distribution of PKDs. Potentially, broadly co-expressed PKD polypeptides may interact to generate homo-or heteromultimeric regulatory complexes. However, the frequency, molecular basis, regulatory significance, and physiological relevance of stable PKD-PKD interactions are largely unknown. Here, we demonstrate that mammalian PKDs 1-3 and the prototypical Caenorhabditis elegans PKD, DKF-2A, are exclusively (homo-or hetero-) dimers in cell extracts and intact cells. We discovered and characterized a novel, highly conserved N-terminal domain, comprising 92 amino acids, which mediates dimerization of PKD1, PKD2, and PKD3 monomers. A similar domain directs DKF-2A homodimerization. Dimerization occurred independently of properties of the regulatory and kinase domains of PKDs. Disruption of PKD dimerization abrogates secretion of PAUF, a protein carried in small trans-Golgi network-derived vesicles. In addition, disruption of DKF-2A homodimerization in C. elegans intestine impaired and degraded the immune defense of the intact animal against an ingested bacterial pathogen. Finally, dimerization was indispensable for the strong, dominant negative effect of catalytically inactive PKDs. Overall, the structural integrity and function of the novel dimerization domain are essential for PKDmediated regulation of a key aspect of cell physiology, secretion, and innate immunity in vivo.The membrane-embedded second messenger diacylglycerol (DAG) 2 mediates actions of many hormones and other stimuli by activating two classes of PKC isoforms (1, 2). Conventional PKCs ␣, ␤I, ␤II, and ␥ are stimulated by DAG and Ca 2ϩ acting in concert; novel PKCs ␦, ⑀, , and are activated by DAG alone. PKCs regulate many aspects of cell physiology by activating members of another family of Ser/Thr kinases, collectively named PKD (3-6). Like PKCs, PKDs have a C-terminal kinase domain that is preceded by C1a and C1b regulatory domains, which bind DAG and a pharmacological activator, phorbol 12-myristate 13-acetate (PMA). C1 domains mediate translocation of PKDs and PKCs from cytoplasm to DAG/PMA-enriched membranes. DAG/PMA-activated PKC phosphorylates the PKD activation loop (A-loop), thereby switching on catalytic activity of the co-recruited D kinase. Thus, PKDs are PKC effectors in regulatory cascades.PKDs diversify DAG/PKC signaling by acting on effectors in plasma membrane, the nucleus, cytoplasm, F-actin cytoskeleton, and cytoplasmic surfaces of mitochondria and Golgi membranes. Because PKCs and PKDs phosphorylate different substrates (3, 4, 7), D kinases place distinct effectors and physiological processes under DAG control. For instance, PKDs mediate pro-survival signaling induced by oxidative stress (8); control ...

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“…Arfaptin1 is required for the export of regulated secretory cargo from the TGN At the TGN, PKD is required for the trafficking of cargoes that contain sorting information for trafficking to the basolateral surface (Yeaman et al, 2004). PKD is also required for the biogenesis of CARTS and secretory storage granules (von Wichert et al, 2008;Wakana et al, 2012). Because PKD phosphorylates and dissociates arfaptin1, we tested the requirement of arfaptins in the PKD-dependent export routes from the TGN.…”

Section: Pkd Phosphorylated Arfaptin1 Does Not Bind the Tgnmentioning

confidence: 99%

Recruitment of arfaptins to the trans-Golgi network by PI(4)P and their involvement in cargo export

Cruz-García

Ortega-Bellido

Scarpa

et al. 2013

EMBO J

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The BAR (Bin/Amphiphysin/Rvs) domain proteins arfaptin1 and arfaptin2 are localized to the trans-Golgi network (TGN) and, by virtue of their ability to sense and/or generate membrane curvature, could play an important role in the biogenesis of transport carriers. We report that arfaptins contain an amphipathic helix (AH) preceding the BAR domain, which is essential for their binding to phosphatidylinositol 4-phosphate (PI(4)P)-containing liposomes and the TGN of mammalian cells. The binding of arfaptin1, but not arfaptin2, to PI(4)P is regulated by protein kinase D (PKD) mediated phosphorylation at Ser100 within the AH. We also found that only arfaptin1 is required for the PKD-dependent trafficking of chromogranin A by the regulated secretory pathway. Altogether, these findings reveal the importance of PI(4)P and PKD in the recruitment of arfaptins at the TGN and their requirement in the events leading to the biogenesis of secretory storage granules.

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Protein kinase D2 regulates chromogranin A secretion in human BON neuroendocrine tumour cells

Cited by 7 publications

References 0 publications

Identification of Mac-2-binding Protein as a Putative Marker of Neuroendocrine Tumors from the Analysis of Cell Line Secretomes

Identification of Mac-2-binding Protein as a Putative Marker of Neuroendocrine Tumors from the Analysis of Cell Line Secretomes

A Novel Conserved Domain Mediates Dimerization of Protein Kinase D (PKD) Isoforms

Recruitment of arfaptins to the trans-Golgi network by PI(4)P and their involvement in cargo export

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