Protein Kinase Cδ Induces Src Kinase Activity via Activation of the Protein Tyrosine Phosphatase PTPα

Brandt, Dominique; Goerke, Axel; Heuer, Marion; Gimona, Mario; Leitges, Michael; Kremmer, Elisabeth; Lammers, Reiner; Haller, Hermann; Mischak, Harald

doi:10.1074/jbc.m211650200

Cited by 87 publications

(75 citation statements)

References 28 publications

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“…This result suggests that TRPC3 is the target of phosphorylation by Src. We can reasonably postulate that Src is getting activated indirectly by PKC, as it was reported in smooth muscle cells [62]. The precise mechanism between PKC activation and TRPC3 opening remains however to be firmly established, but our data suggested that Src is, at least partially, involved in this process.…”

Section: Discussionsupporting

confidence: 81%

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

et al. 2011

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a b s t r a c tThe ER Ca 2+ sensor STIM1 and the Ca 2+ channel Orai1 are key players in store-operated Ca 2+ entry (SOCE). In addition, channels from the TRPC family were also shown to be engaged during SOCE, while their precise implication remains controversial. In this study, we investigated the molecular players involved in SOCE triggered by the SERCA pump inhibitor thapsigargin in an endothelial cell line, the EA.hy926. siRNA directed against STIM1 or Orai1 reduced Ca 2+ entry by about 50-60%, showing that a large part of the entry is independent from these proteins. Blocking the PLC or the PKC pathway completely abolished thapsigargin-induced Ca 2+ entry in cells depleted from STIM1 and/or Orai1. The phorbol ester PMA or the DAG analog OAG restored the Ca 2+ entry inhibited by PLC blockers, showing an involvement of PLC/PKC pathway in SOCE. Using pharmacological inhibitors or siRNA revealed that the PKCeta is required for Ca 2+ entry, and pharmacological inhibition of the tyrosine kinase Src also reduced Ca 2+ entry. TRPC3 silencing diminished the entry by 45%, while the double STIM1/TRPC3 invalidation reduced Ca 2+ entry by more than 85%. Hence, in EA.hy926 cells, TG-induced Ca 2+ entry results from the activation of the STIM1/Orai1 machinery, and from the activation of TRPC3.

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Section: Discussionsupporting

confidence: 81%

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

et al. 2011

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“…PKC␦ Kinase Assay-PKC␦ activity was determined in cell extracts as described (41). Briefly, total PKC␦ was determined by measuring the incorporation of 32 P into MBP.…”

Section: Methodsmentioning

confidence: 99%

Induction of cIAP-2 in Human Colon Cancer Cells through PKCδ/NF-κB

Wang

Evers

2003

Journal of Biological Chemistry

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Activation of protein kinase C (PKC) prevents apoptosis in certain cells; however, the mechanisms are largely unknown. Inhibitors of apoptosis (IAP) family members, including NAIP, cIAP-1, cIAP-2, XIAP/hILP, survivin, and BRUCE, block apoptosis by binding and potently inhibiting caspases. Activation of NF-B contributes to cIAP-2 induction; however, the cellular mechanisms regulating cIAP-2 expression have not been entirely defined. In this study, we examined the role of the PKC and NF-B pathways in the regulation of cIAP-2 in human colon cancers. We found that cIAP-2 mRNA levels were markedly increased in human colon cancer cells by treatment with the phorbol ester, phorbol-12-myristate-13-acetate (PMA), or bryostatin 1. Inhibitors of the Ca 2؉ -independent, novel PKC isoforms, but not inhibitors of MAPK, PI3-kinase, or PKA, blocked PMA-stimulated cIAP-2 mRNA expression, suggesting a role of PKC in PMA-mediated cIAP-2 induction. Pretreatment with the PKC␦-selective inhibitor rottlerin or transfection with an antisense PKC␦ oligonucleotide inhibited PMA-induced cIAP-2 expression, whereas cotransfection with a PKC␦ plasmid induced cIAP-2 promoter activity, which, taken together, identifies a role for PKC␦ in cIAP-2 induction. Treatment with the proteasome inhibitor, MG132 or inhibitors of NF-B (e.g. PDTC and gliotoxin), decreased PMA-induced up-regulation of cIAP-2. PMAinduced NF-B activation was blocked by either GF109203x, MG132, PDTC, or gliotoxin. Moreover, overexpression of PKC␦-induced cIAP-2 promoter activity and increased NF-B transactivation, suggesting regulation of cIAP-2 expression by a PKC␦/NF-B pathway. In conclusion, our findings demonstrate a role for a PKC/NF-B-dependent pathway in the regulation of cIAP-2 expression in human colon cancer cells. These data suggest a novel mechanism for the anti-apoptotic function mediated by the PKC␦/NF-B/cIAP-2 pathway in certain cancers.

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“…Bacterial expression and protein purification: TAT-C3 was produced and purified in Escherichia coli strain DE3 as GST fusion using standard protocols (Brandt et al, 2003).…”

Section: Preparation Of Sema4dmentioning

confidence: 99%

A functional role for semaphorin 4D/plexin B1 interactions in epithelial branching morphogenesis during organogenesis

et al. 2008

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Semaphorins and their receptors, plexins, carry out important functions during development and disease. In contrast to the wellcharacterized plexin A family, however, very little is known about the functional relevance of B-type plexins in organogenesis, particularly outside the nervous system. Here, we demonstrate that plexin B1 and its ligand Sema4d are selectively expressed in epithelial and mesenchymal compartments during key steps in the genesis of some organs. This selective expression suggests a role in epithelial-mesenchymal interactions. Importantly, using the developing metanephros as a model system, we have observed that endogenously expressed and exogenously supplemented Sema4d inhibits branching morphogenesis during early stages of development of the ureteric collecting duct system. Our results further suggest that the RhoA-ROCK pathway, which is activated downstream of plexin B1, mediates these inhibitory morphogenetic effects of Sema4d and suppresses branch-promoting signalling effectors of the plexin B1 signalling complex. Finally, mice that lack plexin B1 show early anomalies in kidney development in vivo. These results identify a novel function for plexin B1 as a negative regulator of branching morphogenesis during kidney development, and suggest that the Sema4d-plexin B1 ligand-receptor pair contributes to epithelial-mesenchymal interactions during organogenesis via modulation of RhoA signalling.

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Protein Kinase Cδ Induces Src Kinase Activity via Activation of the Protein Tyrosine Phosphatase PTPα

Cited by 87 publications

References 28 publications

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

Thapsigargin activates Ca2+ entry both by store-dependent, STIM1/Orai1-mediated, and store-independent, TRPC3/PLC/PKC-mediated pathways in human endothelial cells

Induction of cIAP-2 in Human Colon Cancer Cells through PKCδ/NF-κB

A functional role for semaphorin 4D/plexin B1 interactions in epithelial branching morphogenesis during organogenesis

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