ErbB2 and ErbB4 Cbl binding sites can functionally replace the ErbB1 Cbl binding site

Jansen, Suzanne M.; Sleumer, Laura S.; Damen, Ester; Meijer, Inez M.J.; Zoelen, E.J.J. van; Leeuwen, Jeroen E.M. van

doi:10.1016/j.cellsig.2009.01.028

Cited by 7 publications

(3 citation statements)

References 55 publications

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“…Consistent with this model, the EGFR Y1045F mutant causes EGF to exhibit greater intrinsic activity but does not affect the intrinsic activity of AREG. Indeed, in the presence of the EGFR Y1045F mutant, EGF and AREG exhibit roughly equal intrinsic activity ( Levkowitz et al, 1998 ; Shelly et al, 1998 ; Komurasaki et al, 2002 ; Joslin et al, 2007 ; Gilmore et al, 2008 , 2009 ; Stern et al, 2008 ; Jansen et al, 2009 ; Roepstorff et al, 2009 ; Willmarth et al, 2009 ; Wilson et al, 2009 ; Ahsan et al, 2010 ; Foley et al, 2010 ; Wilson et al, 2012a ; Macdonald-Obermann and Pike, 2014 ; Riese and Cullum, 2014 ; Lemmon et al, 2016 ; Wee and Wang, 2018 ).…”

Section: Structure and Function Of Erbb4mentioning

confidence: 99%

The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein

et al. 2022

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ERBB4 (HER4) is a member of the ERBB family of receptor tyrosine kinases, a family that includes the epidermal growth factor receptor (EGFR/ERBB1/HER1), ERBB2 (Neu/HER2), and ERBB3 (HER3). EGFR and ERBB2 are oncoproteins and validated targets for therapeutic intervention in a variety of solid tumors. In contrast, the role that ERBB4 plays in human malignancies is ambiguous. Thus, here we review the literature regarding ERBB4 function in human malignancies. We review the mechanisms of ERBB4 signaling with an emphasis on mechanisms of signaling specificity. In the context of this signaling specificity, we discuss the hypothesis that ERBB4 appears to function as a tumor suppressor protein and as an oncoprotein. Next, we review the literature that describes the role of ERBB4 in tumors of the bladder, liver, prostate, brain, colon, stomach, lung, bone, ovary, thyroid, hematopoietic tissues, pancreas, breast, skin, head, and neck. Whenever possible, we discuss the possibility that ERBB4 mutants function as biomarkers in these tumors. Finally, we discuss the potential roles of ERBB4 mutants in the staging of human tumors and how ERBB4 function may dictate the treatment of human tumors. Significance Statement This articles reviews ERBB4 function in the context of the mechanistic model that ERBB4 homodimers function as tumor suppressors, whereas ERBB4-EGFR or ERBB4-ERBB2 heterodimers act as oncogenes. Thus, this review serves as a mechanistic framework for clinicians and scientists to consider the role of ERBB4 and ERBB4 mutants in staging and treating human tumors.

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Section: Structure and Function Of Erbb4mentioning

confidence: 99%

The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein

et al. 2022

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“…Curiously, both ErbB2 and ErbB4 contain putative phosphorylation sites with surrounding sequences that are highly homologous to EGFR Y1045. Substitution of these sequences into EGFR preserves EGF-stimulated cbl interaction (84), suggesting that cbl-mediated degradation of activated ErbB2 and ErbB4 may play physiological roles that remain to be delineated. It has also been suggested that ErbB2, ErbB3 and ErbB4 are impaired relative to EGFR in terns of their ligand-induced internalization, down-regulation and degradation (85).…”

Section: Post-transcriptional Regulation Of Erbb Receptor Levelsmentioning

confidence: 99%

E3 ubiquitin ligases in ErbB receptor quantity control

Carraway

2010

Seminars in Cell & Developmental Biology

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Signaling through ErbB family growth factor receptor tyrosine kinases is necessary for the development and homeostasis of a wide variety of tissue types. However, the intensity of receptormediated cellular signaling must fall within a precise range; insufficient signaling can lead to developmental abnormalities or tissue atrophy, while over-signaling can lead to hyperplastic and ultimately neoplastic events. While a plethora of mechanisms have been described that regulate downstream signaling events, it appears that cells also utilize various mechanisms to regulate their ErbB receptor levels. Such mechanisms are collectively termed "ErbB receptor quantity control." Notably, studies over the past few years have highlighted roles for post-transcriptional processes, particularly protein degradation, in ErbB quantity control. Here the involvement of ErbB-directed E3 ubiquitin ligases is discussed, including Nrdp1-mediated ErbB3 degradation, ErbB4 degradation mediated by Nedd4 family E3 ligases, and CHIP-mediated ErbB2 degradation. The hypothesis is forwarded that protein degradation-based ErbB quantity control mechanisms play central roles in suppressing receptor overexpression in normal cells, and that the loss of such mechanisms could facilitate the onset or progression of ErbB-dependent tumors.

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“…Replacing the ErbB1-Cbl-binding site with those of ErbB2 and ErbB4 had no effect on Cbl recruitment, receptor ubiquitination, and clearance, while retrovirus-infected NIH3T3 cells harboring the EGFR-Y1045F mutation dramatically impaired Cbl recruitment, EGFR ubiquitination, and delayed EGFR degradation [50]. These results demonstrated that the c-Cbl-binding sites of ErbB2 and ErbB4 are fully functional, and that the EGFR c-Cbl-binding site was not essential for endosomal trafficking [50]. EGFR was shown to interact directly with the CYT1 and CYT2 variants of ErbB4 and the membrane-anchored intracellular domain.…”

Section: Discussionmentioning

confidence: 97%

c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor

Vogt,

Unnikrishnan,

Heinig

et al. 2023

Cells

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The localization, expression, and physiological role of regulatory proteins in the neurogenic niches of the brain is fundamental to our understanding of adult neurogenesis. This study explores the expression and role of the E3-ubiquitin ligase, c-Cbl, in neurogenesis within the subventricular zone (SVZ) of mice. In vitro neurosphere assays and in vivo analyses were performed in specific c-Cbl knock-out lines to unravel c-Cbl’s role in receptor tyrosine kinase signaling, including the epidermal growth factor receptor (EGFR) pathway. Our findings suggest that c-Cbl is significantly expressed within EGFR-expressing cells, playing a pivotal role in neural stem cell proliferation and differentiation. However, c-Cbl’s function extends beyond EGFR signaling, as its loss upon knock-out stimulated progenitor cell proliferation in neurosphere cultures. Yet, this effect was not detected in hippocampal progenitor cells, reflecting the lack of the EGFR in the hippocampus. In vivo, c-Cbl exerted only a minor proneurogenic influence with no measurable impact on the formation of adult-born neurons. In conclusion, c-Cbl regulates neural stem cells in the subventricular zone via the EGFR pathway but, likely, its loss is compensated by other signaling modules in vivo.

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ErbB2 and ErbB4 Cbl binding sites can functionally replace the ErbB1 Cbl binding site

Cited by 7 publications

References 55 publications

The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein

The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein

E3 ubiquitin ligases in ErbB receptor quantity control

c-Cbl Regulates Murine Subventricular Zone-Derived Neural Progenitor Cells in Dependence of the Epidermal Growth Factor Receptor

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