RETRACTED: Cytohesins Are Cytoplasmic ErbB Receptor Activators

Bill, Anke; Schmitz, Anton; Albertoni, Barbara; Song, Jian; Heukamp, Lukas C.; Walrafen, David; Thorwirth, Franziska; Verveer, Peter J.; Zimmer, Sebastian; Meffert, Lisa; Schreiber, Arne; Chatterjee, Sampurna; Thomas, Roman K.; Ullrich, Roland T.; Lang, Thorsten; Famulok, Michael

doi:10.1016/j.cell.2010.09.011

Cited by 72 publications

(83 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This does not exclude other functions of cytohesins, e.g. the stabilization of asymmetric ErbB (EGFR) dimers, as shown recently in human lung and breast adenosarcoma cancer cell lines (Bill et al, 2010). Our data indicate, however, that a major function of the Drosophila cytohesin Step in EGFR signaling resides downstream of the EGFR and upstream of MAPK.…”

Section: Discussioncontrasting

confidence: 76%

“…Bill et al could show that cytohesin 2 is a cytoplasmic ErbB receptor activator by stabilizing active asymmetric ErbB dimers (Bill et al, 2010). Interestingly, our data point towards a more downstream role of…”

Section: Steppke Controls Egfr/mapk Signaling 2473supporting

confidence: 55%

“…Recent studies in human lung and breast adenosarcoma cancer cell lines indicated a function of cytohesins in ErbB (EGFR) signaling, where they facilitate signaling by stabilizing an asymmetric ErbB receptor dimer (Bill et al, 2010). Here we provide the first in vivo model that the cytohesin Step, in addition to its previously characterized function as component of IIS, regulates EGFR signaling dependent wing growth and vein differentiation.…”

Section: Introductionmentioning

confidence: 88%

See 2 more Smart Citations

The drosophila Arf GEF steppke controls MAPK activation in EGFR signaling

Hahn

Fuss

Peters

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryGuanine nucleotide exchange factors (GEFs) of the cytohesin protein family are regulators of GDP/GTP exchange for members of the ADP ribosylation factor (Arf) of small GTPases. They have been identified as modulators of various receptor tyrosine kinase signaling pathways including the insulin, the vascular epidermal growth factor (VEGF) and the epidermal growth factor (EGF) pathways. These pathways control many cellular functions, including cell proliferation and differentiation, and their misregulation is often associated with cancerogenesis. In vivo studies on cytohesins using genetic loss of function alleles are lacking, however, since knockout mouse models are not available yet. We have recently identified mutants for the single cytohesin Steppke (Step) in Drosophila and we could demonstrate an essential role of Step in the insulin signaling cascade. In the present study, we provide in vivo evidence for a role of Step in EGFR signaling during wing and eye development. By analyzing step mutants, transgenic RNA interference (RNAi) and overexpression lines for tissue specific as well as clonal analysis, we found that Step acts downstream of the EGFR and is required for the activation of mitogen-activated protein kinase (MAPK) and the induction of EGFR target genes. We further demonstrate that step transcription is induced by EGFR signaling whereas it is negatively regulated by insulin signaling. Furthermore, genetic studies and biochemical analysis show that Step interacts with the Connector Enhancer of KSR (CNK). We propose that Step may be part of a larger signaling scaffold coordinating receptor tyrosine kinase-dependent MAPK activation.

show abstract

Section: Discussioncontrasting

confidence: 76%

Section: Steppke Controls Egfr/mapk Signaling 2473supporting

confidence: 55%

Section: Introductionmentioning

confidence: 88%

See 1 more Smart Citation

The drosophila Arf GEF steppke controls MAPK activation in EGFR signaling

Hahn

Fuss

Peters

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Previous work by others has identified other cytoplasmic activators of EGF receptor tyrosine kinases, such as YES (Yamaguchi sarcoma virus oncogene) and cytohesins (26)(27)(28). However, their roles in EGFR activation are limited.…”

Section: Discussionmentioning

confidence: 99%

“…However, their roles in EGFR activation are limited. YES-mediated EGFR phosphorylation occurs only on the endosome, mildly increases phosphorylation on limited sites, and requires EGF stimulation and pIgA-pIgR transcytosis (26,27). Furthermore, cytohesins do not influence receptor dimerization but function as conformational activators of dimerized receptors after EGF stimulation (26,27).…”

Section: Discussionmentioning

confidence: 99%

Plakophilin-2 Promotes Tumor Development by Enhancing Ligand-Dependent and -Independent Epidermal Growth Factor Receptor Dimerization and Activation

Arimoto

Burkart

Yan

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

Epidermal growth factor (EGF) receptor (EGFR) has been implicated in tumor development and invasion. Dimerization and autophosphorylation of EGFR are the critical events for EGFR activation. However, the regulation of EGF-dependent and EGFindependent dimerization and phosphorylation of EGFR has not been fully understood. Here, we report that cytoplasmic protein plakophilin-2 (PKP2) is a novel positive regulator of EGFR signaling. PKP2 specifically interacts with EGFR via its N-terminal head domain. Increased PKP2 expression enhances EGF-dependent and EGF-independent EGFR dimerization and phosphorylation. Moreover, PKP2 knockdown reduces EGFR phosphorylation and attenuates EGFR-mediated signal activation, resulting in a significant decrease in proliferation and migration of cancer cells and tumor development. Our results indicate that PKP2 is a novel activator of the EGFR signaling pathway and a potential new drug target for inhibiting tumor growth.

show abstract

Attacking the supply wagons to starve cancer cells to death

et al. 2016

View full text Add to dashboard Cite

The constitutive anabolism of cancer cells supports proliferation but also addicts tumor cells to a steady influx of exogenous nutrients. Limiting access to metabolic substrates could be an effective and selective means to block cancer growth. In this review, we define the pathways by which cancer cells acquire the raw materials for anabolism, highlight the actionable proteins in each pathway, and discuss the status of therapeutic interventions that disrupt nutrient acquisition. Critical open questions to be answered before apical metabolic inhibitors can be successfully and safely deployed in the clinic are also outlined. In summary, recent studies provide strong support that substrate limitation is a powerful therapeutic strategy to effectively, and safely, starve cancer cells to death.

show abstract

RETRACTED: Cytohesins Are Cytoplasmic ErbB Receptor Activators

Cited by 72 publications

References 56 publications

The drosophila Arf GEF steppke controls MAPK activation in EGFR signaling

The drosophila Arf GEF steppke controls MAPK activation in EGFR signaling

Plakophilin-2 Promotes Tumor Development by Enhancing Ligand-Dependent and -Independent Epidermal Growth Factor Receptor Dimerization and Activation

Attacking the supply wagons to starve cancer cells to death

Contact Info

Product

Resources

About