scholarly journals Epidermal Growth Factor Receptor Acts as a Negative Regulator for Bacterium Nontypeable Haemophilus influenzae-induced Toll-like Receptor 2 Expression via an Src-dependent p38 Mitogen-activated Protein Kinase Signaling Pathway

2005 ◽  
Vol 280 (43) ◽  
pp. 36185-36194 ◽  
Author(s):  
Fumi Mikami ◽  
He Gu ◽  
Hirofumi Jono ◽  
Ali Andalibi ◽  
Hirofumi Kai ◽  
...  
Keyword(s):  
Immune Response ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Host Defense ◽  
Growth Factor Receptor ◽  
Negative Regulation ◽  
Negative Regulator ◽  
Egfr Signaling ◽  
Epidermal Growth

Epidermal growth factor receptor (EGFR) has been shown to play important roles in regulating diverse biological processes, including cell growth, differentiation, apoptosis, adhesion, and migration. Its role in regulating human Toll-like receptors (TLRs), key host defense receptors that recognize invading bacterial pathogens, however, remains unknown. Here we show for the first time that EGFR acts as a negative regulator for TLR2 induction by the bacterium nontypeable Haemophilus influenzae (NTHi) in vitro and in vivo. The negative regulation of TLR2 induction by EGFR is mediated via an Src-MKK3/6-p38 α/β MAP kinase-dependent mechanism. Moreover, direct activation of EGFR signaling by the bacterium NTHi-derived EGF-like factor appears to be responsible for triggering the downstream Src-MKK3/6-p38 MAPK signaling, which in turn leads to the negative regulation of TLR2 induction. Finally, exogenous EGF increases NTHi invasion of host epithelial cells, thereby demonstrating the biological significance of TLR2 regulation by EGFR signaling. The evidence we provided in the present study may suggest a novel strategy utilized by bacteria to attenuate host defensive and immune response by negatively regulating the expression of host defense receptor TLR2. These studies may bring new insight for fully understanding the important role of EGFR signaling in regulating host defense and immune response by tightly controlling TLR2 induction during bacterial infections.

The epidermal growth factor receptor ligand amphiregulin is a negative regulator of hepatic acute-phase gene expression

2009 ◽  
Vol 51 (6) ◽  
pp. 1010-1020 ◽  
Author(s):  
Ana Pardo-Saganta ◽  
Maria Ujue Latasa ◽  
Josefa Castillo ◽  
Laura Alvarez-Asiain ◽  
María J. Perugorría ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Acute Phase ◽  
Growth Factor Receptor ◽  
Negative Regulator ◽  
Receptor Ligand ◽  
Epidermal Growth

scholarly journals CG6015 controls spermatogonia transit-amplifying divisions by epidermal growth factor receptor signaling in Drosophila testes

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Jun Yu ◽  
Qianwen Zheng ◽  
Zhiran Li ◽  
Yunhao Wu ◽  
Yangbo Fu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Stem Cell ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Gene Set Enrichment Analysis ◽  
Germline Stem Cell ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Epidermal Growth

AbstractSpermatogonia transit-amplifying (TA) divisions are crucial for the differentiation of germline stem cell daughters. However, the underlying mechanism is largely unknown. In the present study, we demonstrated that CG6015 was essential for spermatogonia TA-divisions and elongated spermatozoon development in Drosophila melanogaster. Spermatogonia deficient in CG6015 inhibited germline differentiation leading to the accumulation of undifferentiated cell populations. Transcriptome profiling using RNA sequencing indicated that CG6015 was involved in spermatogenesis, spermatid differentiation, and metabolic processes. Gene Set Enrichment Analysis (GSEA) revealed the relationship between CG6015 and the epidermal growth factor receptor (EGFR) signaling pathway. Unexpectedly, we discovered that phosphorylated extracellular regulated kinase (dpERK) signals were activated in germline stem cell (GSC)-like cells after reduction of CG6015 in spermatogonia. Moreover, Downstream of raf1 (Dsor1), a key downstream target of EGFR, mimicked the phenotype of CG6015, and germline dpERK signals were activated in spermatogonia of Dsor1 RNAi testes. Together, these findings revealed a potential regulatory mechanism of CG6015 via EGFR signaling during spermatogonia TA-divisions in Drosophila testes.

Epidermal growth factor receptor (EGFR) signaling in cancer

Gene ◽  
2006 ◽  
Vol 366 (1) ◽  
pp. 2-16 ◽  
Author(s):  
Nicola Normanno ◽  
Antonella De Luca ◽  
Caterina Bianco ◽  
Luigi Strizzi ◽  
Mario Mancino ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Epidermal Growth

scholarly journals The Ubiquitin-like Protein PLIC-2 Is a Negative Regulator of G Protein-coupled Receptor Endocytosis

2008 ◽  
Vol 19 (3) ◽  
pp. 1252-1260 ◽  
Author(s):  
Elsa-Noah N'Diaye ◽  
Aylin C. Hanyaloglu ◽  
Kimberly K. Kajihara ◽  
Manojkumar A. Puthenveedu ◽  
Ping Wu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
G Protein ◽  
Growth Factor Receptor ◽  
Negative Regulator ◽  
Regulatory Function ◽  
Receptor Endocytosis ◽  
Epidermal Growth ◽  
G Protein Coupled

The activity of many signaling receptors is regulated by their endocytosis via clathrin-coated pits (CCPs). For G protein-coupled receptors (GPCRs), recruitment of the adaptor protein arrestin to activated receptors is thought to be sufficient to drive GPCR clustering in CCPs and subsequent endocytosis. We have identified an unprecedented role for the ubiquitin-like protein PLIC-2 as a negative regulator of GPCR endocytosis. Protein Linking IAP to Cytoskeleton (PLIC)-2 overexpression delayed ligand-induced endocytosis of two GPCRs: the V2 vasopressin receptor and β-2 adrenergic receptor, without affecting endocytosis of the transferrin or epidermal growth factor receptor. The closely related isoform PLIC-1 did not affect receptor endocytosis. PLIC-2 specifically inhibited GPCR concentration in CCPs, without affecting membrane recruitment of arrestin-3 to activated receptors or its cellular levels. Depletion of cellular PLIC-2 accelerated GPCR endocytosis, confirming its regulatory function at endogenous levels. The ubiquitin-like domain of PLIC-2, a ligand for ubiquitin-interacting motifs (UIMs), was required for endocytic inhibition. Interestingly, the UIM-containing endocytic adaptors epidermal growth factor receptor protein substrate 15 and Epsin exhibited preferential binding to PLIC-2 over PLIC-1. This differential interaction may underlie PLIC-2 specific effect on GPCR endocytosis. Identification of a negative regulator of GPCR clustering reveals a new function of ubiquitin-like proteins and highlights a cellular requirement for exquisite regulation of receptor dynamics.

scholarly journals Epidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 Endocytosis

2020 ◽  
Vol 94 (11) ◽  
Author(s):  
Carina Bannach ◽  
Pia Brinkert ◽  
Lena Kühling ◽  
Lilo Greune ◽  
M. Alexander Schmidt ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Endocytic Pathway ◽  
Egfr Signaling ◽  
Endocytic Vesicle ◽  
Human Papillomavirus 16 ◽  
Epidermal Growth

ABSTRACT Human papillomavirus 16 (HPV16), the leading cause of cervical cancer, exploits a novel endocytic pathway during host cell entry. This mechanism shares many requirements with macropinocytosis but differs in the mode of vesicle formation. Previous work indicated a role of the epidermal growth factor receptor (EGFR) in HPV16 endocytosis. However, the functional outcome of EGFR signaling and its downstream targets during HPV16 uptake are not well characterized. Here, we analyzed the functional importance of signal transduction via EGFR and its downstream effectors for endocytosis of HPV16. Our findings indicate two phases of EGFR signaling as follows: a—likely dispensable—transient activation with or shortly after cell binding and signaling required throughout the process of asynchronous internalization of HPV16. Interestingly, EGFR inhibition interfered with virus internalization and strongly reduced the number of endocytic pits, suggesting a role for EGFR signaling in the induction of HPV16 endocytosis. Moreover, we identified the Src-related kinase Abl2 as a novel regulator of virus uptake. Inhibition of Abl2 resulted in an accumulation of misshaped endocytic pits, indicating Abl2’s importance for endocytic vesicle maturation. Since Abl2 rather than Src, a regulator of membrane ruffling during macropinocytosis, mediated downstream signaling of EGFR, we propose that the selective effector targeting downstream of EGFR determines whether HPV16 endocytosis or macropinocytosis is induced. IMPORTANCE Human papillomaviruses are small, nonenveloped DNA viruses that infect skin and mucosa. The so-called high-risk HPVs (e.g., HPV16, HPV18, HPV31) have transforming potential and are associated with various anogenital and oropharyngeal tumors. These viruses enter host cells by a novel endocytic pathway with unknown cellular function. To date, it is unclear how endocytic vesicle formation occurs mechanistically. Here, we addressed the role of epidermal growth factor receptor signaling, which has previously been implicated in HPV16 endocytosis and identified the kinase Abl2 as a novel regulator of virus uptake. Since other viruses, such as influenza A virus and lymphocytic choriomeningitis virus, possibly make use of related mechanisms, our findings shed light on fundamental strategies of virus entry and may in turn help to develop new host cell-targeted antiviral strategies.

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