Protein Kinase D Signaling

Rozengurt, Enrique; Rey, Osvaldo; Waldron, Richard T.

doi:10.1074/jbc.r500002200

Cited by 414 publications

(547 citation statements)

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“…Wnt5a induced the phosphorylation of protein kinase D (PKD)/PKCm in DU145 cells (Figure 4b). PKD is a protein kinase, which not only is a direct target of diacylglycerol but also lies downstream of novel PKCs (Rozengurt et al, 2005). Therefore, these results suggested that Wnt5a activates novel PKCs.…”

Section: Mechanism Of Wnt5a-induced Invasion By Pca Cellsmentioning

confidence: 77%

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

et al. 2010

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Wnt5a is a representative ligand that activates the b-catenin-independent pathway in Wnt signaling. Although it has been reported that abnormal activation of the Wnt/ b-catenin-dependent pathway is often observed in human prostate cancer, the involvement of the b-catenin-independent pathway in this cancer is unclear. Abnormal expression of Wnt5a and b-catenin was observed in 27 (28%) and 49 (50%) of 98 prostate cancer cases, respectively, by immunohistochemical analyses. Simultaneous expression of Wnt5a and b-catenin was observed in only five cases, suggesting their exclusive expression. The positive detection of Wnt5a was correlated with high Gleason scores and biochemical relapse of prostate cancer, but that of b-catenin was not. Knockdown and overexpression of Wnt5a in human prostate cancer cell lines reduced and stimulated, respectively, their invasion activities, and the invasion activity required Frizzled2 and Ror2 as Wnt receptors. Wnt5a activated Jun-N-terminal kinase through protein kinase D (PKD) and the inhibition of PKD suppressed Wnt5a-dependent cell migration and invasion. In addition, Wnt5a induced the expression of metalloproteinase-1 through the recruitment of JunD to its promoter region. These results suggest that Wnt5a promotes the aggressiveness of prostate cancer and that its expression is involved in relapse after prostatectomy.

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Section: Mechanism Of Wnt5a-induced Invasion By Pca Cellsmentioning

confidence: 77%

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

et al. 2010

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“…Protein kinase D (PKD) represents a family (PKCμ/PKD1, PKD2, and PKCv/PKD3) of CAMK-related protein kinases with distinct structural, enzymological and dynamic properties [6]. PKDs, as well as several protein kinase C (PKC) isoforms, are directly stimulated by the second messenger diacylglycerol.…”

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confidence: 99%

“…PKDs, as well as several protein kinase C (PKC) isoforms, are directly stimulated by the second messenger diacylglycerol. Further, PKDs have emerged as effectors of novel PKC isoforms including PKCε and PKCη, which directly phosphorylate and activate PKDs in novel protein kinase cascades [6,7]. PKD, activated via PKC-mediated activation loop phosphorylation, exhibits dynamic spatiotemporal behavior including nucleocytoplasmic shuttling [6].…”

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confidence: 99%

Identification of a novel phosphorylation site in c-jun directly targeted in vitro by protein kinase D

Waldron

Whitelegge

Faull

2007

Biochemical and Biophysical Research Communications

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Protein kinase D (PKD) phosphorylates the c-jun amino-terminal in vitro at site(s) distinct from JNK [C. Hurd, R.T. Waldron, E. Rozengurt, Protein kinase D complexes with c-jun N-terminal kinase via activation loop phosphorylation and phosphorylates the c-jun N-terminus, Oncogene 21 (2002) 2154-2160], but the sites have not been identified. Here, metabolic 32 P-labeling of c-jun protein in COS-7 cells indicated that PKD phosphorylates c-jun in vivo at a site(s) between aa 43-93, a region containing important functional elements. On this basis, the PKD-mediated phosphorylation site(s) was further characterized in vitro using GST-c-jun fusion proteins. PKD did not incorporate phosphate into Ser63 and Ser73, the JNK sites in GST-c-jun(1-89). Rather, PKD and JNK could sequentially phosphorylate distinct site(s) simultaneously. By mass spectrometry of tryptic phosphopeptides, Ser58 interposed between the JNK-binding portion of the delta domain and the adjacent TAD1 was identified as a prominent site phosphorylated in vitro by PKD. These data were further supported by kinase reactions using truncations or point-mutations of GST-c-jun. Together, these data suggest that PKD-mediated phosphorylation modulates c-jun at the level of its N-terminal functional domains.

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“…They are activated by the actions of hormones, growth factors, neurotransmitters, and other stimuli through phospholipase C (PLC) [1] . Three widely-expressed mammalian homologs are PKD1 (mouse PKD, human PKCμ) [2,3] , PKD2 [3] , and PKD3 [4] (also named PKC), but the levels of individual PKDs vary in different tissues.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase D: a new player among the signaling proteins that regulate functions in the nervous system

Wang

2014

Neurosci. Bull.

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Protein kinase D (PKD) is an evolutionarily-conserved family of protein kinases. It has structural, regulatory, and enzymatic properties quite different from the PKC family. Many stimuli induce PKD signaling, including G-protein-coupled receptor agonists and growth factors. PKD1 is the most studied member of the family. It functions during cell proliferation, differentiation, secretion, cardiac hypertrophy, immune regulation, angiogenesis, and cancer. Previously, we found that PKD1 is also critically involved in pain modulation. Since then, a series of studies performed in our lab and by other groups have shown that PKDs also participate in other processes in the nervous system including neuronal polarity establishment, neuroprotection, and learning. Here, we discuss the connections between PKD structure, enzyme function, and localization, and summarize the recent fi ndings on the roles of PKD-mediated signaling in the nervous system. Keywords: PKD; neuronal polarity; pain modulation; neuroprotection; learning IntroductionMembers of the protein kinase D (PKD) family are diacylglycerol (DAG) and protein kinase C (PKC) effectors.They are activated by the actions of hormones, growth factors, neurotransmitters, and other stimuli through phospholipase C (PLC) [1] . Three widely-expressed mammalian homologs are PKD1 (mouse PKD, human PKCμ) [2,3] , PKD2 [3] , and PKD3 [4] (also named PKC), but the levels of individual PKDs vary in different tissues.Recent fi ndings have revealed that PKDs participate in the regulation of Golgi function through modulating the fi ssion of vesicles from the trans-Golgi network (TGN) [5,6] . Other recent reports have shown that PKDs function during cell proliferation and apoptosis, carcinogenesis, and intracellular trafficking. Here, we describe the connections between PKD structure, enzymatic function, and localization, and then summarize recent fi ndings on the roles of PKD in the nervous system. The PKD Family Belongs to the CaMK GroupThe PKD family comprises PKD1, PKD2, and PKD3. PKD was initially described as an atypical isoform of the PKC family [7] , which is a member of the protein kinase A, G, and C (AGC) serine/threonine kinase subfamily [8,9] . However, later studies revealed that PKD has mixed features of different subclasses of the PKC family, so it does not belong to any one of them. For example, its pleckstrin-homology (PH) domain is closely related to the PKB and G-proteincoupled receptor kinase (GRK) families and is not found in any PKC enzyme, while the cysteine-rich domains are more reminiscent of classical and novel PKCs. The structure and function of the catalytic domain of PKD are quite different from those of the AGC/PKC family members [2][3][4]10] . Indeed, PKD has now been classified as a new family within the (Fig. 1). The elaborate constitution of PKD1 is intricately linked to its catalytic functions, regulation, and intracellular localization (Table 1). PKD1 can be activated through different pathways.First, some stimuli activate PLC, which induces PKD phosp...

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Protein Kinase D Signaling

Cited by 414 publications

References 82 publications

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase

Identification of a novel phosphorylation site in c-jun directly targeted in vitro by protein kinase D

Protein kinase D: a new player among the signaling proteins that regulate functions in the nervous system

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