scholarly journals Extracellular ATP stimulates the early growth response protein 1 (Egr-1) via a protein kinase C-dependent pathway in the human osteoblastic HOBIT cell line

2003 ◽  
Vol 373 (3) ◽  
pp. 815-824 ◽  
Author(s):  
Alex PINES ◽  
Milena ROMANELLO ◽  
Laura CESARATTO ◽  
Giuseppe DAMANTE ◽  
Luigi MORO ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Cytosolic Calcium ◽  
Early Growth ◽  
Extracellular Atp ◽  
Extracellular Nucleotides ◽  
Cell Physiology ◽  
Early Growth Response ◽  
Kinase C

Extracellular nucleotides exert an important role in controlling cell physiology by activating intracellular signalling cascades. Osteoblast HOBIT cells express P2Y1 and P2Y2 G-protein-coupled receptors, and respond to extracellular ATP by increasing cytosolic calcium concentrations. Early growth response protein 1 (Egr-1) is a C2H2-zinc-finger-containing transcriptional regulator responsible for the activation of several genes involved in the control of cell proliferation and apoptosis, and is thought to have a central role in osteoblast biology. We show that ATP treatment of HOBIT cells increases Egr-1 protein levels and binding activity via a mechanism involving a Ca2+-independent protein kinase C isoform. Moreover, hypotonic stress and increased medium turbulence, by inducing ATP release, result in a similar effect on Egr-1. Increased levels of Egr-1 protein expression and activity are achieved at very early times after stimulation (5 min), possibly accounting for a rapid way for changing the osteoblast gene-expression profile. A target gene for Egr-1 that is fundamental in osteoblast physiology, COL1A2, is up-regulated by ATP stimulation of HOBIT cells in a timescale that is compatible with that of Egr-1 activation.

scholarly journals Protein Kinase C β/Early Growth Response-1 Pathway

2006 ◽  
Vol 48 (9) ◽  
pp. A47-A55 ◽  
Author(s):  
Shi-Fang Yan ◽  
Evis Harja ◽  
Martin Andrassy ◽  
Tomoyuki Fujita ◽  
Ann Marie Schmidt
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response ◽  
Kinase C ◽  
Early Growth Response 1

scholarly journals The Protein Kinase C System Acts through the Early Growth Response Protein 1 to Increase LHβ Gene Expression in Synergy with Steroidogenic Factor-1

1999 ◽  
Vol 13 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Lisa M. Halvorson ◽  
Ursula B. Kaiser ◽  
William W. Chin
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Gene Promoter ◽  
Early Growth ◽  
Mrna Levels ◽  
Steroidogenic Factor 1 ◽  
Early Growth Response ◽  
Kinase C

Abstract Expression of the LHβ gene has been shown to be modulated by both the orphan nuclear receptor, steroidogenic factor-1 (SF-1), and the early growth response protein 1, Egr-1. It is also well known that LHβ mRNA levels are increased after hormonal activation of the protein kinase C (PKC) signaling system, for example by GnRH; however, the mechanisms by which the PKC system exerts this effect has not been fully characterized. By transient transfection of the GH3 cell line, we demonstrate that activation of the PKC system with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), increases activity of region −207/+5 of the rat LHβ gene promoter (∼2-fold) and markedly augments SF-1-induced stimulation (95-fold in the presence of both factors vs. 13-fold for SF-1 alone). Mutation of the two previously identified Egr-1 sites not only prevents Egr-1 effects on the LHβ gene promoter, but also eliminates the synergistic response to PMA and SF-1 together, findings that were confirmed in a longer construct spanning region −797/+5. In the gonadotrope-derived cell line,α T3–1, these mutations eliminate the GnRH responsiveness of the− 207/+5 LHβ promoter construct. We next show that PMA treatment (GH3 and αT3–1 cells) or GnRH treatment (αT3–1 cells) induces expression of Egr-1, as detected by Egr-1 interaction with Egr-1 DNA-binding sites in the rat LHβ gene promoter sequence. Furthermore, we demonstrate that PMA increases steady-state Egr-1 mRNA levels via increased Egr-1 transcription. We conclude that PMA-induced stimulation of LHβ gene expression is achieved, at least in part, by induction of Egr-1 expression.

PDGF-induced mitogenic signaling is not mediated through protein kinase C and c-fos pathway in VSM cells

1993 ◽  
Vol 264 (1) ◽  
pp. C71-C79 ◽  
Author(s):  
R. V. Sharma ◽  
R. C. Bhalla
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Dna Synthesis ◽  
Thymidine Incorporation ◽  
Cytosolic Calcium ◽  
Platelet Derived Growth Factor ◽  
Kinase C ◽  
Pdgf Stimulation ◽  
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.

Ca2+ mobilization by extracellular ATP in rat cardiac myocytes: regulation by protein kinase C and A

1992 ◽  
Vol 263 (5) ◽  
pp. C933-C940 ◽  
Author(s):  
J. S. Zheng ◽  
A. Christie ◽  
M. N. Levy ◽  
A. Scarpa
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ventricular Myocytes ◽  
Cell Voltage ◽  
Extracellular Atp ◽  
Camp Level ◽  
Intracellular Camp ◽  
Beta Adrenergic ◽  
Kinase C ◽  
Integrated Response

Activation of protein kinase C (PKC) modulates the mobilization of intracellular Ca2+ induced by extracellular ATP in rat ventricular myocytes. Pretreatment of myocytes with PKC activators attenuated both the ATP-induced Ca2+ transient and the noradrenergic potentiation of the Ca2+ response. Various PKC activators decreased both the basal cAMP level and the cAMP levels that had been elevated by norepinephrine, forskolin, or 3-isobutyl-1-methylxanthine. The inhibitory effects of PKC activators were reversed by the PKC inhibitor staurosporine. The ATP-induced Ca2+ response is an integrated response resulting from ATP eliciting an inward cation current (IATP), cellular depolarization, Ca2+ influx through Ca2+ channels, and Ca2+ release from the sarcoplasmic reticulum. We used the whole cell voltage-clamp technique to investigate which steps of this integrated response are affected by PKC. PKC activators did not significantly affect the IATP. In contrast, PKC activators decreased the basal Ca2+ current (ICa) or Ba2+ current and the beta-adrenergic-stimulated ICa. These results suggest that PKC-induced suppression of the ATP-induced Ca2+ response and the beta-adrenergic-potentiated Ca2+ response is achieved at least partially by decreasing the intracellular cAMP level and ICa.

Protein kinase C is involved in enhanced airway smooth muscle cell growth in hyperresponsive rats

2000 ◽  
Vol 278 (1) ◽  
pp. L59-L67 ◽  
Author(s):  
M. E. Zacour ◽  
J. G. Martin
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Growth ◽  
Airway Smooth Muscle ◽  
Western Blotting ◽  
Growth Response ◽  
Airway Smooth Muscle Cell ◽  
Kinase C ◽  
Potential Risk Factors

Fischer rat airway smooth muscle (ASM) models two potential risk factors for asthma: hyperresponsiveness to contractile agonists and to growth stimuli. The aim of this study was to identify the mechanisms responsible for enhanced ASM mitogenic response in Fischer rats compared with the control Lewis strain. The enhanced Fischer ASM cell growth response to fetal bovine serum (FBS) could not be accounted for by phospholipase C, mitogen-activated protein kinases, or tyrosine kinase activities as assessed by pharmacological inhibition and Western blotting. In contrast, depletion of phorbol ester-sensitive isoforms of the serine/threonine kinase protein kinase C (PKC) removed the difference in growth response between the rat strains. Additionally, FBS selectively induced serine/threonine phosphorylation of a 115-kDa protein in Fischer ASM cells. Enhanced activation of PKC-βI and decreased activation of PKC-δ in Fischer compared with Lewis cells following FBS stimulation were suggested by Western blotting of membrane and cytosolic fractions. The data are consistent with a role for PKC in the enhanced ASM cell growth of hyperresponsive rats.

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