The EGFR/ERBB Receptor Family

Pareja, Fresia; Pines, Gur; Yarden, Yosef

doi:10.1007/978-3-319-11888-8_4

Cited by 5 publications

(4 citation statements)

References 381 publications

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“…The epidermal growth factor (EGF) receptor (EGFR) is a receptor tyrosine kinase that controls many aspects of development and adult physiology, which at the cellular level involves enhancement of survival, growth, and proliferation ( Avraham and Yarden, 2011 ; Pareja et al, 2015 ). EGFR must be tightly regulated, and dysregulation of this receptor has important roles in driving the growth and progression of certain cancers ( Sigismund et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Fyn and TOM1L1 are recruited to clathrin-coated pits and regulate Akt signaling

Cabral-Dias

Lucarelli

Zak

et al. 2022

Journal of Cell Biology

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The epidermal growth factor (EGF) receptor (EGFR) controls many aspects of cell physiology. EGF binding to EGFR elicits the membrane recruitment and activation of phosphatidylinositol-3-kinase, leading to Akt phosphorylation and activation. Concomitantly, EGFR is recruited to clathrin-coated pits (CCPs), eventually leading to receptor endocytosis. Previous work uncovered that clathrin, but not receptor endocytosis, is required for EGF-stimulated Akt activation, and that some EGFR signals are enriched in CCPs. Here, we examine how CCPs control EGFR signaling. The signaling adaptor TOM1L1 and the Src-family kinase Fyn are enriched within a subset of CCPs with unique lifetimes and protein composition. Perturbation of TOM1L1 or Fyn impairs EGF-stimulated phosphorylation of Akt2 but not Akt1. EGF stimulation also triggered the TOM1L1- and Fyn-dependent recruitment of the phosphoinositide 5-phosphatase SHIP2 to CCPs. Thus, the recruitment of TOM1L1 and Fyn to a subset of CCPs underlies a role for these structures in the support of EGFR signaling leading to Akt activation.

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Section: Introductionmentioning

confidence: 99%

Fyn and TOM1L1 are recruited to clathrin-coated pits and regulate Akt signaling

Cabral-Dias

Lucarelli

Zak

et al. 2022

Journal of Cell Biology

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“…Other groups identified pTyr-EGFR in lung tumor biopsies using IHC with antibodies specific for one of the six pTyr-EGFR docking sites: pTyr-845, -1045, -1068, -1086, -1148, and -1173 [55]. Kanematsu et al showed that phosphorylation, but not EGFR overexpression, is associated with poor prognosis of NSCLC using an antibody against pTyr845 [56].…”

Section: Discussionmentioning

confidence: 99%

Detection of Activated Receptor Tyrosine Kinases in Human Lung Squamous Cell Carcinoma

Kendrick

Hoelter

Koll

et al. 2023

Preprint

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Lung squamous cell carcinoma (LSCC) has a high mutational burden and poor prognosis, even with immunotherapy. In the Lux-Lung 8 trial, afatinib, an epidermal growth factor receptor (EGFR) inhibitor, showed a long-term benefit in 5.3% of patients with LSCC. Because activating mutations of EGFR are rare in LSCC, the response was likely due to wild-type EGFR being activated by an unknown mechanism. All receptor tyrosine kinase (RTK) proteins, both wild-type and mutated, are activated by phosphorylation of specific tyrosines which serve as binding sites for various SH2 proteins. The aim of this feasibility study was to determine whether enhanced chemiluminescent western blotting (WB) with a phosphotyrosine (pTyr) antibody is sufficiently sensitive to detect pTyr-RTK proteins in human LSCC tissues. We performed WB analysis on 25 resected human lung tissue samples, including 12 LSCC, two adenocarcinomas (LADC), and 11 control (non-tumor) lung samples. The analysis showed ~220 kDa pTyr-protein bands in two LSCC samples that were much more abundant than the corresponding bands in controls or LADC samples. To identify pTyr-RTKs, pTyr WB patterns of the two samples were compared to those of five RTK candidates: EGFR, platelet-derived growth factor receptor beta (PDGFRB), vascular endothelial growth factor receptor, anaplastic lymphoma receptor, and mesenchymal-epithelial transition factor. The strong pTyr signal in one sample matched EGFR, whereas the other matched a combination of EGFR and PDGFRB. We conclude that pTyr WB is sufficiently sensitive to detect pTyr-RTK drivers in flash-frozen tumor tissues and might identify LSCC patient subsets responsive to RTK inhibitors.

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“…An important future question is to identify the receptor of the NRG1 ligand. Strong candidates are the ErbB family of proteins known to function as NRG1 receptors in other tissues including the brain [57,58]. Interestingly, ErbB gene 4 (ERBB4) has been identified in GWAS studies of both human obesity [59] and diabetic kidney disease [60,61].…”

Section: Discussionmentioning

confidence: 99%