scholarly journals Bile acid stimulation of early growth response gene and mitogen-activated protein kinase is protein kinase C-dependent

1996 ◽  
Vol 316 (3) ◽  
pp. 765-769 ◽  
Author(s):  
Lynda M. BRADY ◽  
David W. A. BENO ◽  
Bernard H. DAVIS
Keyword(s):  
Bile Acid ◽  
Protein Kinase ◽  
Bile Acids ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein

Hepatic stellate cells are exposed to elevated bile acid levels during hepatic injury and fibrogenesis. Upon activation, the stellate cell becomes a major effector cell during the development of hepatic fibrosis and cirrhosis. Bile acids may function as co-stimulatory signalling molecules. This hypothesis was tested in vitro using rat-derived hepatic stellate cells. Bile acids were studied at concentrations that occur during cirrhosis in vivo. Conjugated and unconjugated bile acids rapidly induced egr and fos gene expression as well as cytoplasmic mitogen-activated protein kinase (MAPK) activation. Protein kinase C was required for both egr induction and MAPK activation. These studies imply that bile acids could contribute to the perpetuation of hepatic fibrosis by helping to keep the stellate cell in an activated state.

scholarly journals Diacylglycerol generated by exogenous phospholipase C activates the mitogen-activated protein kinase pathway independent of Ras- and phorbol ester-sensitive protein kinase C: dependence on protein kinase C-ζ

1997 ◽  
Vol 323 (3) ◽  
pp. 693-699 ◽  
Author(s):  
Marc C. M. van DIJK ◽  
Francisco J. G. MURIANA ◽  
Paul C. J. van der HOEVEN ◽  
John de WIDT ◽  
Dick SCHAAP ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Phorbol Ester ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Pkc Ζ

The role of diacylglycerol (DG) formation from phosphatidylcholine in mitogenic signal transduction is poorly understood. We have generated this lipid at the plasma membrane by treating Rat-1 fibroblasts with bacterial phosphatidylcholine-specific phospholipase C (PC-PLC). This treatment leads to activation of mitogen-activated protein kinase (MAPK). However, unlike platelet-derived growth factor (PDGF) or epidermal growth factor (EGF), PC-PLC fails to activate Ras and to induce DNA synthesis, and activates MAPK only transiently (< 45 min). Down-regulation of protein kinase C (PKC) -α, -Δ and -ε isotypes has little or no effect on MAPK activation by either PC-PLC or growth factors. However, Ro 31-8220, a highly selective inhibitor of all PKC isotypes, including atypical PKC-ζ but not Raf-1, blocks MAPK activation by PDGF and PC-PLC, but not that by EGF, suggesting that atypical PKC mediates the PDGF and PC-PLC signal. In line with this, PKC-ζ is activated by PC-PLC and PDGF, but not by EGF, as shown by a kinase assay in vitro, using biotinylated ε-peptide as a substrate. Furthermore, dominant-negative PKC-ζ inhibits, while (wild-type) PKC-ζ overexpression enhances MAPK activation by PDGF and PC-PLC. The results suggest that DG generated by PC-PLC can activate the MAPK pathway independent of Ras and phorbol-ester-sensitive PKC but, instead, via PKC-ζ.

scholarly journals High glucose activates rat pancreatic stellate cells through protein kinase C and p38 mitogen-activated protein kinase pathway

Suizo ◽  
2007 ◽  
Vol 22 (5) ◽  
pp. 595-597
Author(s):  
Yoko Nomiyama ◽  
Mitsuo Tashiro ◽  
Taizo Yamaguchi ◽  
Shiro Watanabe ◽  
Masashi Taguchi ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
High Glucose ◽  
Stellate Cells ◽  
Mitogen Activated Protein Kinase ◽  
Pancreatic Stellate Cells ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals Ca2+ and protein kinase C-dependent mechanisms involved in gastrin-induced Shc/Grb2 complex formation and P44-mitogen-activated protein kinase activation

1997 ◽  
Vol 325 (2) ◽  
pp. 383-389 ◽  
Author(s):  
Laurence DAULHAC ◽  
Aline KOWALSKI-CHAUVEL ◽  
Lucien PRADAYROL ◽  
Nicole VAYSSE ◽  
Catherine SEVA
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Phosphorylation ◽  
Phorbol Esters ◽  
Receptor Occupancy ◽  
Mitogen Activated Protein Kinase ◽  
Free Calcium ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein

The proliferative effects of gastrin on normal and neoplastic gastro-intestinal tissues have been shown to be mediated by the gastrin/CCKB (G/CCKB) G-protein-coupled receptors. We have recently reported that gastrin stimulates the tyrosine phosphorylation of Shc proteins and their subsequent association with the Grb2/Sos complex, leading to mitogen-activated protein kinase (MAPK) activation, a pathway known to play an important role in cell proliferation. We undertook the present study to characterize the signalling pathways used by this receptor to mediate the activation of the Shc/Grb2 complex. Since G/CCKB receptor occupancy leads to the activation of the phospholipase C (PLC)/protein kinase C (PKC) pathway, we examined whether PKC stimulation and Ca2+ mobilization contribute to the phosphorylation of Shc proteins and their association with Grb2 in response to gastrin. Our results indicate that Shc proteins are tyrosine phosphorylated and associate with Grb2 in response to phorbol esters, suggesting that activation of PKC is a potential signalling pathway leading to activation of the Shc/Grb2 complex. Inhibition of PKC by GF109203X completely blocked the effect of PMA on Shc tyrosine phosphorylation and its subsequent association with Grb2, but had a partial inhibitory effect on the response to gastrin. Depletion of the intracellular Ca2+ pools by treatment with thapsigargin blocked the increase in intracellular free calcium concentration induced by gastrin and diminished the ability of the peptide to stimulate Shc phosphorylation and recruitment of Grb2. In addition, removal of extracellular Ca2+ partially inhibited the effect of gastrin on Shc phosphorylation as well as its association with Grb2, indicating that the effects of gastrin are also mediated by Ca2+-dependent mechanisms. Furthermore, we show that blockage of the two major early signals generated by activation of PLC, which induced the activation of the Shc/Grb2 complex, also blocked gastrin-induced MAPK activation.

scholarly journals Angiotensin II Activates Mitogen-Activated Protein Kinase Via Protein Kinase C and Ras/Raf-1 Kinase in Bovine Adrenal Glomerulosa Cells

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1801-1809 ◽  
Author(s):  
Ying Tian ◽  
Roger D. Smith ◽  
Tamas Balla ◽  
Kevin J. Catt
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Time Course ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Glomerulosa Cells

Abstract Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10–50 pm. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.

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