Pharmacological modulation of amyloid precursor protein (APP) secretion from neuronal cell lines and primary neuronal cultures: Role of protein kinase C (PKC) activation

This study examines the role of protein kinase C (PKC) in platelet-derived growth factor (PDGF)-induced vascular smooth muscle (VSM) cell proliferation and initial signaling events. A 24-h pretreatment of VSM cells with 200 nM phorbol 12-myristate 13-acetate (PMA) completely abolished immunologically reactive PKC activity. Depletion of PKC activity from VSM cells did not attenuate PDGF-stimulated [3H]thymidine incorporation compared with control cells. Similarly, acute activation of PKC by treatment with 200 nM PMA for 10 min had no effect on PDGF-mediated [3H]thymidine incorporation. Both PMA and PDGF increased c-fos induction to the same magnitude; however, treatment with PMA did not induce DNA synthesis in these cells. In PKC-depleted cells PDGF-mediated c-fos induction was reduced by 50-60%, while DNA synthesis in response to PDGF stimulation was not reduced. PKC depletion did not alter PDGF-stimulated increase in cytosolic calcium levels, 125I-PDGF binding, or receptor autophosphorylation. On the basis of these results, we conclude that PKC activation and c-fos induction do not play a significant role in PDGF-mediated mitogenesis in VSM cells.

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Protein kinase C regulates endocytosis and recycling of E-cadherin

AJP Cell Physiology ◽

10.1152/ajpcell.00566.2001 ◽

2002 ◽

Vol 283 (2) ◽

pp. C489-C499 ◽

Cited By ~ 85

Author(s):

Tam Luan Le ◽

Shannon R. Joseph ◽

Alpha S. Yap ◽

Jennifer L. Stow

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Phorbol Esters ◽

Recycling Endosomes ◽

Kinase C ◽

Pkc Isozymes ◽

Pkc Activation ◽

Darby Canine Kidney ◽

E Cadherin

E-cadherin is a major component of adherens junctions in epithelial cells. We showed previously that a pool of cell surface E-cadherin is constitutively internalized and recycled back to the surface. In the present study, we investigated the potential role of protein kinase C (PKC) in regulating the trafficking of surface E-cadherin in Madin-Darby canine kidney cells. Using surface biotinylation and immunofluorescence, we found that treatment of cells with phorbol esters increased the rate of endocytosis of E-cadherin, resulting in accumulation of E-cadherin in apically localized early or recycling endosomes. The recycling of E-cadherin back to the surface was also decreased in the presence of phorbol esters. Phorbol ester-induced endocytosis of E-cadherin was blocked by specific inhibitors, implicating novel PKC isozymes, such as PKC-ε in this pathway. PKC activation led to changes in the actin cytoskeleton facilitating E-cadherin endocytosis. Depolymerization of actin increased endocytosis of E-cadherin, whereas the PKC-induced uptake of E-cadherin was blocked by the actin stabilizer jasplakinolide. Our findings show that PKC regulates vital steps of E-cadherin trafficking, its endocytosis, and its recycling.

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Phorbol 12,13-Diacetate-Induced Contraction of the Canine Basilar Artery: Role of Protein Kinase C

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.16 ◽

1991 ◽

Vol 11 (1) ◽

pp. 135-142 ◽

Cited By ~ 44

Author(s):

Makoto Sugawa ◽

Tohru Koide ◽

Shigetaka Naitoh ◽

Michiaki Takato ◽

Tohru Matsui ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Normal Medium ◽

Kinase C ◽

Prostaglandin F ◽

Basilar Arteries ◽

Canine Basilar Artery ◽

Biochemical Mechanisms ◽

Pkc Activation

The pharmacological and biochemical mechanisms of contractile responses to the protein kinase C (PKC) activator phorbol-12, 13-diacetate (PDA) were investigated in canine basilar arteries, In the normal medium, PDA elicited a strong, dose-related, and slow-developing sustained contraction, Among the constrictors examined, including serotonin, prostaglandin F2α and endothelin, only PDA yielded contractions in a 2 Ca2+ -free medium, In both media, the PDA-induced contractions were virtually inhibited by either staurosporine, H-7, or quinacrine, while neither neurotransmitter blockades nor R24571 (calmidazolium) exerted significant effects, In addition, it was shown that 8-bromocyclic GMP, but not 8-bromocyclic AMP, markedly curtailed the PDA-induced contractions, Biochemical analysis, furthermore, showed that PDA induced increased phosphorylations of 27- and 96-kDa and proteins other than the myosin light chain (MLC) 20-kDa protein, Thus, the present results open up a novel mechanism of sustained cerebral artery contractions, where PKC activation rather than Ca2+/calmodulin/MLC system plays a key role that is regulated both by phospholipase A 2 and by cyclic GMP.

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Immunocytochemical localization of protein kinase C in developing brain tissue and in primary neuronal cultures

Developmental Biology ◽

10.1016/0012-1606(88)90243-6 ◽

1988 ◽

Vol 126 (1) ◽

pp. 98-107 ◽

Cited By ~ 18

Author(s):

Peggy R. Girard ◽

John G. Wood ◽

Joseph E. Freschi ◽

J.F. Kuo

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Brain Tissue ◽

Developing Brain ◽

Neuronal Cultures ◽

Immunocytochemical Localization ◽

Primary Neuronal Cultures ◽

Kinase C

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Protein kinase A modulates Ca2+- and protein kinase C-dependent amylase release in permeabilized rat pancreatic acini

Biochemical Journal ◽

10.1042/bj2870403 ◽

1992 ◽

Vol 287 (2) ◽

pp. 403-406 ◽

Cited By ~ 15

Author(s):

A J O'Sullivan ◽

J D Jamieson

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Protein Kinase A ◽

Response Curve ◽

Amylase Release ◽

Pancreatic Acini ◽

Kinase C ◽

Pkc Activation ◽

Kinase A

The role of protein kinase A (PKA) in the release of amylase from permeabilized pancreatic acini was investigated. Addition of cyclic AMP (cAMP) to permeabilized acini resulted in a potentiation of Ca(2+)-dependent amylase release, shifting the Ca2+ dose/response curve leftwards. As with protein kinase C (PKC) activation, this is due to an increase in the time of active discharge. The effect of cAMP was shown to be blocked by two inhibitors of PKA, H89 and the PKI-(5-24)-peptide. At low concentration, cAMP synergizes from phorbol 12-myristate 13-acetate (PMA), while at optimal concentrations cAMP and PMA are additive. PKA and PKC appear to work via similar, but not identical mechanisms.

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