Physiological functions of protein kinase D <i>in vivo</i>

Ellwanger, Kornelia; Haußer, Angelika

doi:10.1002/iub.1116

Cited by 38 publications

(37 citation statements)

References 82 publications

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“…Clearly, mouse skin is not a useful model to study PKD functions in human epidermis. These differences are likely reflective of major structural and functional differences between mouse and human skin as well as the contextdependent functions of PKDs (2,6). Contrary to mouse skin, we found PKD signaling to be essential for maintaining human epidermal homeostasis.…”

Section: Discussionmentioning

confidence: 56%

“…involved in the regulation of diverse biological and pathological processes including cell proliferation and differentiation, adhesion and migration, protein transport, cell survival, angiogenesis, and tumor cell proliferation and metastasis (1,2). Aberrant PKD activity and expression have been shown in a number of tumors including breast, skin, prostate, and pancreatic cancers (3)(4)(5).…”

mentioning

confidence: 99%

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Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Ryvkin

Rashel

Gaddapara

et al. 2015

Journal of Biological Chemistry

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Background:The role of protein kinase D (PKD) signaling in human epidermis is unclear. Results: PKD isoforms have distinct and opposing growth regulatory functions in human keratinocytes. PKD3 is down-regulated upon differentiation and PKD3 silencing results in loss of keratinocyte proliferative potential. Conclusion: PKD signaling is essential for maintaining human epidermal homeostasis. Significance: PKD3 represents a potential drug target in hyperproliferative skin disorders.

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Ryvkin

Rashel

Gaddapara

et al. 2015

Journal of Biological Chemistry

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“…Recently, apoptosis mediated by ER stress was demonstrated to contribute to the progression of diabetic cardiomyopathy [6][7][8]. http Protein kinase D (PKD) is a recent addition to the calcium/calmodulin-dependent protein kinase (CAMK) group of serine/threonine kinases, increasingly implicated in the regulation of multiple cell biological processes, including cell survival, migration, differentiation, and proliferation [9,10]. Recent advances demonstrate an important role of PKD-mediated signaling pathways in the cardiovascular system, particularly in the regulation of myocardial contraction and hypertrophy [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Irbesartan ameliorates diabetic cardiomyopathy by regulating protein kinase D and ER stress activation in a type 2 diabetes rat model

Liu

Wang

et al. 2015

Pharmacological Research

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“…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)(4)(5)(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).…”

mentioning

confidence: 99%

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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Physiological functions of protein kinase D in vivo

Cited by 38 publications

References 82 publications

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Opposing Growth Regulatory Roles of Protein Kinase D Isoforms in Human Keratinocytes

Irbesartan ameliorates diabetic cardiomyopathy by regulating protein kinase D and ER stress activation in a type 2 diabetes rat model

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

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