Ubiquitination switches EphA2 vesicular traffic from a continuous safeguard to a finite signalling mode

Pasquale, E. B. Eph-ephrin bidirectional signaling in physiology and disease. Cell 133, 38–52 (2008) .

Nievergall, E., Lackmann, M. & Janes, P. W. Eph-dependent cell-cell adhesion and segregation in development and cancer. Cell Mol. Life Sci. 69, 1813–1842 (2012) .

Klein, R. Eph/ephrin signalling during development. Development 139, 4105–4109 (2012) .

Halloran, M. C. & Wolman, M. A. Repulsion or adhesion: receptors make the call. Curr. Opin. Cell Biol. 18, 533–540 (2006) .

Lackmann, M. & Boyd, A. W. Eph, a protein family coming of age: more confusion, insight, or complexity? Sci. Signal 1, re2 (1)–re2 (16) (2008) .

Lemmon, M. A. & Schlessinger, J. Cell signaling by receptor-tyrosine kinases. Cell 141, 1117–1134 (2010) .

Wiesner, S. et al. A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases. EMBO J. 25, 4686–4696 (2006) .

Wybenga-Groot, L. E. et al. Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region. Cell 106, 745–757 (2001) .

Binns, K. L., Taylor, P. P., Sicheri, F., Pawson, T. & Holland, S. J. Phosphorylation of tyrosine residues in the kinase domain and juxtamembrane region regulates the biological and catalytic activities of Eph receptors. Mol. Cell Biol. 20, 4791–4805 (2000) .

Davis, T. L. et al. Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure 16, 873–884 (2008) .

Chen, H. et al. Cracking the molecular origin of intrinsic tyrosine kinase activity through analysis of pathogenic gain-of-function mutations. Cell Rep. 4, 376–384 (2013) .

Zelinski, D. P., Zantek, N. D., Stewart, J. C., Irizarry, A. R. & Kinch, M. S. EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res. 61, 2301–2306 (2001) .

Pasquale, E. B. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat. Rev. Cancer 10, 165–180 (2010) .

Zantek, N. D. et al. E-cadherin regulates the function of the EphA2 receptor tyrosine kinase. Cell Growth Differ. 10, 629–638 (1999) .

Reynolds, A. R., Tischer, C., Verveer, P. J., Rocks, O. & Bastiaens, P. I. EGFR activation coupled to inhibition of tyrosine phosphatases causes lateral signal propagation. Nat. Cell Biol. 5, 447–453 (2003) .

Wimmer-Kleikamp, S. H. et al. Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells. Blood 112, 721–732 (2008) .

Shintani, T. et al. Eph receptors are negatively controlled by protein tyrosine phosphatase receptor type O. Nat. Neurosci. 9, 761–769 (2006) .

Poliakov, A., Cotrina, M. L., Pasini, A. & Wilkinson, D. G. Regulation of EphB2 activation and cell repulsion by feedback control of the MAPK pathway. J. Cell Biol. 183, 933–947 (2008) .

Nievergall, E. et al. PTP1B regulates Eph receptor function and trafficking. J. Cell Biol. 191, 1189–1203 (2010) .

Haj, F. G. et al. Regulation of signaling at regions of cell-cell contact by endoplasmic reticulum-bound protein-tyrosine phosphatase 1B. PLoS One 7, e36633 (2012) .

Fischer, E. H., Charbonneau, H. & Tonks, N. K. Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes. Science 253, 401–406 (1991) .

Zhang, Z. Y., Maclean, D., Thieme-Sefler, A. M., Roeske, R. W. & Dixon, J. E. A continuous spectrophotometric and fluorimetric assay for protein tyrosine phosphatase using phosphotyrosine-containing peptides. Anal. Biochem. 211, 7–15 (1993) .

Yudushkin, I. A. et al. Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of PTP1B. Science 315, 115–119 (2007) .

Haj, F. G., Verveer, P. J., Squire, A., Neel, B. G. & Bastiaens, P. I. H. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the endoplasmic reticulum. Science 295, 1708–1711 (2002) .

Endres, N. F. et al. Conformational coupling across the plasma membrane in activation of the EGF receptor. Cell 152, 543–556 (2013) .

Sawano, A., Takayama, S., Matsuda, M. & Miyawaki, A. Lateral propagation of EGF signaling after local stimulation is dependent on receptor density. Dev. Cell 3, 245–257 (2002) .

Goh, L. K. & Sorkin, A. Endocytosis of receptor tyrosine kinases. Cold Spring Harb. Perspect. Biol. 5, a017459 (2013) .

Scita, G. & Di Fiore, P. P. The endocytic matrix. Nature 463, 464–473 (2010) .

Wouters, F. S., Verveer, P. J. & Bastiaens, P. I. Imaging biochemistry inside cells. Trends Cell. Biol. 11, 203–211 (2001) .

Walther, K. A., Papke, B., Sinn, M. B., Michel, K. & Kinkhabwala, A. Precise measurement of protein interacting fractions with fluorescence lifetime imaging microscopy. Mol. Biosyst. 7, 322–336 (2011) .

Kirchner, J., Kam, Z., Tzur, G., Bershadsky, A. D. & Geiger, B. Live-cell monitoring of tyrosine phosphorylation in focal adhesions following microtubule disruption. J. Cell Sci. 116, 975–986 (2003) .

Miao, H. et al. Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat. Cell Biol. 3, 527–530 (2001) .

Miao, H. et al. EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell 16, 9–20 (2009) .

Walker-Daniels, J., Riese, D. J. & Kinch, M. S. c-Cbl-dependent EphA2 protein degradation is induced by ligand binding. Mol. Cancer Res. 1, 79–87 (2002) .

Fasen, K., Cerretti, D. P. & Huynh-Do, U. Ligand binding induces Cbl-dependent EphB1 receptor degradation through the lysosomal pathway. Traffic 9, 251–266 (2008) .

Boissier, P., Chen, J. & Huynh-Do, U. EphA2 signaling following endocytosis: role of Tiam1. Traffic 14, 1255–1271 (2013) .

Seiradake, E., Harlos, K., Sutton, G., Aricescu, A. R. & Jones, E. Y. An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. Nat. Struct. Mol. Biol. 17, 398–402 (2010) .

Himanen, J. P. et al. Architecture of Eph receptor clusters. Proc. Natl Acad. Sci. USA 107, 10860–10865 (2010) .

Squire, A., Verveer, P. J., Rocks, O. & Bastiaens, P. I. Red-edge anisotropy microscopy enables dynamic imaging of homo-FRET between green fluorescent proteins in cells. J. Struct. Biol. 147, 62–69 (2004) .

Haj, F. G., Markova, B., Klaman, L. D., Bohmer, F. D. & Neel, B. G. Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1B. J. Biol. Chem. 278, 739–744 (2003) .

Anderie, I., Schulz, I. & Schmid, A. Direct interaction between ER membrane-bound PTP1B and its plasma membrane-anchored targets. Cell Signal 19, 582–592 (2007) .

Ullrich, O., Reinsch, S., Urbe, S., Zerial, M. & Parton, R. G. Rab11 regulates recycling through the pericentriolar recycling endosome. J. Cell Biol. 135, 913–924 (1996) .

Patterson, G. H. & Lippincott-Schwartz, J. A photoactivatable GFP for selective photolabeling of proteins and cells. Science 297, 1873–1877 (2002) .

Flint, A. J., Tiganis, T., Barford, D. & Tonks, N. K. Development of "substrate-trapping" mutants to identify physiological substrates of protein tyrosine phosphatases. Proc. Natl Acad. Sci. USA 94, 1680–1685 (1997) .

Bucci, C. et al. The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell 70, 715–728 (1992) .

den Hertog, J., Groen, A. & van der Wijk, T. Redox regulation of protein-tyrosine phosphatases. Arch. Biochem. Biophys. 434, 11–15 (2005) .

Vanlandingham, P. A. & Ceresa, B. P. Rab7 regulates late endocytic trafficking downstream of multivesicular body biogenesis and cargo sequestration. J. Biol. Chem. 284, 12110–12124 (2009) .

Chen, J. W., Murphy, T. L., Willingham, M. C., Pastan, I. & August, J. T. Identification of two lysosomal membrane glycoproteins. J. Cell Biol. 101, 85–95 (1985) .

Meng, W., Sawasdikosol, S., Burakoff, S. J. & Eck, M. J. Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase. Nature 398, 84–90 (1999) .

Wang, Y. et al. Negative regulation of EphA2 receptor by Cbl. Biochem. Biophys. Res. Commun. 296, 214–220 (2002) .

Sharfe, N., Freywald, A., Toro, A. & Roifman, C. M. Ephrin-a1 induces, c-Cbl phosphorylation and EphA receptor down-regulation in T cells. J. Immunol. 170, 6024–6032 (2003) .

Yang, N. Y. et al. Crosstalk of the EphA2 receptor with a serine/threonine phosphatase suppresses the Akt-mTORC1 pathway in cancer cells. Cell Signal 23, 201–212 (2011) .

Barbieri, M. A. et al. Epidermal growth factor and membrane trafficking: EGF receptor activation of endocytosis requires Rab5a. J. Cell Biol. 151, 539–550 (2000) .

Poteryaev, D., Datta, S., Ackema, K., Zerial, M. & Spang, A. Identification of the switch in early-to-late endosome transition. Cell 141, 497–508 (2010) .

Raiborg, C. et al. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nat. Cell Biol. 4, 394–398 (2002) .

Ravid, T., Sweeney, C., Gee, P., Carraway, K. L. 3rd & Goldkorn, T. Epidermal growth factor receptor activation under oxidative stress fails to promote c-Cbl mediated down-regulation. J. Biol. Chem. 277, 31214–31219 (2002) .

Petrelli, A. et al. The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature 416, 187–190 (2002) .

Soubeyran, P., Kowanetz, K., Szymkiewicz, I., Langdon, W. Y. & Dikic, I. Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature 416, 183–187 (2002) .

Wimmer-Kleikamp, S. H., Janes, P. W., Squire, A., Bastiaens, P. I. H. & Lackmann, M. Recruitment of Eph receptors into signaling clusters does not require ephrin contact. J. Cell Biol. 164, 661–666 (2004) .

Grecco, H. n. E., Schmick, M. & Bastiaens, P. I. H. Signaling from the living plasma membrane. Cell 144, 897–909 (2011) .

Tischer, C. & Bastiaens, P. I. Lateral phosphorylation propagation: an aspect of feedback signalling? Nat. Rev. Mol. Cell Biol. 4, 971–974 (2003) .

Eden, E. R., White, I. J., Tsapara, A. & Futter, C. E. Membrane contacts between endosomes and ER provide sites for PTP1B-epidermal growth factor receptor interaction. Nat. Cell Biol. 12, 267–272 (2010) .

Schaupp, A. et al. The composition of EphB2 clusters determines the strength in the cellular repulsion response. J. Cell Biol. 204, 409–422 (2014) .

Pabbisetty, K. B. et al. Kinetic analysis of the binding of monomeric and dimeric ephrins to Eph receptors: correlation to function in a growth cone collapse assay. Protein Sci. 16, 355–361 (2007) .

Huyer, G. et al. Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate. J. Biol. Chem. 272, 843–851 (1997) .

Sigismund, S. et al. Threshold-controlled ubiquitination of the EGFR directs receptor fate. EMBO J. 32, 2140–2157 (2013) .