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

1999 ◽  
Vol 13 (1) ◽  
pp. 106-116 ◽  
Author(s):  
L. M. Halvorson
Keyword(s):  
Gene Expression ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Growth Response ◽  
Early Growth ◽  
Steroidogenic Factor 1 ◽  
Early Growth Response ◽  
Kinase C

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.

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
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