Mapping ErbB receptors on breast cancer cell membranes during signal transduction

Yang, Shujie; Raymond-Stintz, Mary Ann; Ying, Wenxia; Zhang, Jun; Lidke, Diane S.; Steinberg, Stanly; Williams, Lance R.; Oliver, Janet M.; Wilson, Bridget S.

doi:10.1242/jcs.007658

Cited by 90 publications

(128 citation statements)

References 54 publications

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“…ERBB3 expressed in stably transfected CHO cells formed clusters in the cell membrane. 95 The sizes of these clusters were similar with high or low receptor expression, and increased when NRG was added. In SKBR3 mammary carcinoma cells, NRG also led to large increases in ERBB3 clusters and marked coclustering of ERBB3 with the p85 subunit of PI3K, but not with ERBB2 or EGFR.…”

Section: Erbb3 Interacting Proteins: Activation Signaling and Regulamentioning

confidence: 89%

The ERBB3 receptor in cancer and cancer gene therapy

2008

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ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase/AKT survival/mitogenic pathway, but also with GRB, SHC, SRC, ABL, rasGAP, SYK and the transcription regulator EBP1. There are likely important but poorly understood roles for nuclear localization and for secreted isoforms. Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung. Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers. Thus a wide and centrally important role for ERBB3 in cancer is becoming increasingly apparent. Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma.

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Section: Erbb3 Interacting Proteins: Activation Signaling and Regulamentioning

confidence: 89%

The ERBB3 receptor in cancer and cancer gene therapy

2008

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“…Thus, it is not possible to determine whether specific predimers of these receptors exist. Because these two receptors appear to be spatially segregated (49), ErbB2/ErbB3 predimer formation may be quite low.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Analysis of the Epidermal Growth Factor (EGF) Receptor-ErbB2-ErbB3 Protein Network by Luciferase Fragment Complementation Imaging

Macdonald-Obermann

Adak

Landgraf

et al. 2013

Journal of Biological Chemistry

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Background:The EGF receptor, ErbB2, and ErbB3 can interact to form dimers. Results: Analyses of these interactions show that ErbB3 interacts strongly with ErbB2 but weakly with the EGF receptor. All ErbB receptor interactions are enhanced by erlotinib and lapatinib. Conclusion: ErbB3 binds and is functionally affected by tyrosine kinase inhibitors. Significance: Tyrosine kinase inhibitors restructure the network of ErbB interactions.

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“…Experimental and theoretical investigation of EGF binding [3,9,17] emphasized the importance of spatial distribution of receptors. Ample experimental evidence indicates that EGF receptors can have a highly inhomogeneous distribution characterized by small areas of high density [30], and exhibit anomalous diffusion [20]. There are other examples of receptors that exhibit clustering and anomalous diffusion [1].…”

Section: The Microscopic Picturementioning

confidence: 99%

The impact of high density receptor clusters on VEGF signaling

Chen

Short

Halász

et al. 2013

Electron. Proc. Theor. Comput. Sci.

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Vascular endothelial growth factor (VEGF) signaling is involved in the process of blood vessel development and maintenance. Signaling is initiated by binding of the bivalent VEGF ligand to the membrane-bound receptors (VEGFR), which in turn stimulates receptor dimerization. Herein, we discuss experimental evidence that VEGF receptors localize in caveloae and other regions of the plasma membrane, and for other receptors, it has been shown that receptor clustering has an impact on dimerization and thus also on signaling. Overall, receptor clustering is part of a complex ecosystem of interactions and how receptor clustering impacts dimerization is not well understood. To address these questions, we have formulated the simplest possible model. We have postulated the existence of a single high affinity region in the cell membrane, which acts as a transient trap for receptors. We have defined an ODE model by introducing high-and low-density receptor variables and introduce the corresponding reactions from a realistic model of VEGF signal initiation. Finally, we use the model to investigate the relation between the degree of VEGFR concentration, ligand availability, and signaling. In conclusion, our simulation results provide a deeper understanding of the role of receptor clustering in cell signaling.

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Mapping ErbB receptors on breast cancer cell membranes during signal transduction

Cited by 90 publications

References 54 publications

The ERBB3 receptor in cancer and cancer gene therapy

The ERBB3 receptor in cancer and cancer gene therapy

Dynamic Analysis of the Epidermal Growth Factor (EGF) Receptor-ErbB2-ErbB3 Protein Network by Luciferase Fragment Complementation Imaging

The impact of high density receptor clusters on VEGF signaling

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