The Host Cell Transcription Factor EGR1 Is Induced by Bacteria through the EGFR–ERK1/2 Pathway

Abstract

The essential first step in bacterial colonization is adhesion to the host epithelial cells. The early host-responses post-bacterial adhesions are still poorly understood. Early growth response 1 (EGR1) is an early response transcriptional regulator that can be rapidly induced by various environmental stimuli. Several bacteria can induce EGR1 expression in host cells, but the involved bacterial characteristics and the underlying molecular mechanisms of this response are largely unknown. Here, we show that EGR1 can be induced in host epithelial cells by different species of bacteria independent of the adherence level, Gram-staining type and pathogenicity. However, bacterial viability and contact with host cells is necessary, indicating that an active interaction between bacteria and the host is important. Furthermore, the strongest response is observed in cells originating from the natural site of the infection, suggesting that the EGR1 induction is cell type specific. Finally, we show that EGFR–ERK1/2 and β1-integrin signaling are the main pathways used for bacteria-mediated EGR1 upregulation. In conclusion, the increase of EGR1 expression in epithelial cells is a common stress induced, cell type specific response upon host-bacteria interaction that is mediated by EGFR–ERK1/2 and β1-integrin signaling.

Activating transcription factor 3 modulates the macrophage immune response toMycobacterium tuberculosisinfection via reciprocal regulation of inflammatory genes and lipid body formation

“…It is ubiquitously expressed and is induced upon challenge of a variety of cell types by bacteria (de Klerk, Saroj, Wassing, Maudsdotter, & Jonsson, 2017). It is ubiquitously expressed and is induced upon challenge of a variety of cell types by bacteria (de Klerk, Saroj, Wassing, Maudsdotter, & Jonsson, 2017).…”

“…EGR1 is a zinc-finger TF that is expressed as an immediate early gene in response to external signals that regulate cell physiology including growth, differentiation, and survival. It is ubiquitously expressed and is induced upon challenge of a variety of cell types by bacteria (de Klerk, Saroj, Wassing, Maudsdotter, & Jonsson, 2017). Previous reports have shown that EGR1 regulates ATF3 expression in murine αT3-1 cells (Mayer, Dexheimer, Nishida, Kitajima, & Thiel, 2008).…”

Comparative transcriptomic analysis identifies reprogramming and differentiation genes differentially expressed in UiPSCs and ESCs

“…Teichroeb et al found that NNAT was consistently silenced in iPSCs compared with its isogenic ESCs, and suppression of NNAT could be used as a biomarker for successful reprogramming (17). EGR1 is a zinc-finger pro-differentiation factor that plays an important role in the regulation of differentiation and development in several contexts (19). Recently, Worringer et al suggested that EGR1 might be a barrier to reprogramming of let-7, and inhibition EGR1 mRNA by RNA-binding protein (RBP) LIN-41 could promote reprogramming (18).…”

Protein Kinase D3 promotes the cell proliferation by activating the ERK1/c‐MYC axis in breast cancer

“…The integrated phosphoproteomic and transcriptomic analysis in the previous studies showed that PRKD3 may play important roles in a variety of the cancer-related pathways. [17][18][19][20][21][22][23] These ERK1/2-activated downstream factors further regulate many cellular functions, including proliferation, differentiation and transformation. 2,12 However, the interaction mechanisms among PRKD3, ERK1 and c-MYC in cancer cells has not been well-investigated since only one prostate cancer study suggested PRKD3-activated ERK1/2 is involved in tumour growth.…”

“…[14][15][16] Activated ERK1/2 translocates to the cell nucleus and then phosphorylates a series of transcription factors, such as c-MYC, FOS, FRA1 and EGR1. [17][18][19][20][21][22][23] These ERK1/2-activated downstream factors further regulate many cellular functions, including proliferation, differentiation and transformation. [24][25][26] In mammals, the identity of ERK1 and ERK2 sequences is 84%, but ERK1 has two more amino acids (a.a.) at its C-terminus and 17 more a.a. at N-terminus than ERK2.…”