Differential Effects of EGFR Ligands on Endocytic Sorting of the Receptor

Endocytic downregulation is a pivotal mechanism turning off signalling from the EGF receptor (EGFR). It is well established that whereas EGF binding leads to lysosomal degradation of EGFR, transforming growth factor (TGF)‐α causes receptor recycling. TGF‐α therefore leads to continuous signalling and is a more potent mitogen than EGF. In addition to EGF and TGF‐α, five EGFR ligands have been identified. Although many of these ligands are upregulated in cancers, very little is known about their effect on EGFR trafficking.

[1]  J. M. Mullin.  Epithelial Barriers, Compartmentation, and Cancer , 2004, Science's STKE.

[2]  A. Sorkin,et al.  Growth factor receptor binding protein 2-mediated recruitment of the RING domain of Cbl to the epidermal growth factor receptor is essential and sufficient to support receptor endocytosis. , 2005, Molecular biology of the cell.

[3]  R. Derynck,et al.  Epidermal growth factor and transforming growth factor-alpha: differential intracellular routing and processing of ligand-receptor complexes. , 1991, Cell regulation.

[4]  I. Madshus,et al.  Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation. , 2004, Experimental cell research.

[5]  M. Nau,et al.  cbl-b inhibits epidermal growth factor receptor signaling , 1999, Oncogene.

[6]  P. Jänne,et al.  Autocrine Production of Amphiregulin Predicts Sensitivity to Both Gefitinib and Cetuximab in EGFR Wild-type Cancers , 2008, Clinical Cancer Research.

[7]  A Ciechanover,et al.  Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1. , 1999, Molecular cell.

[8]  F. Révillion,et al.  ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  Y. Yarden,et al.  A mutant EGF‐receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling , 2002, The EMBO journal.

[10]  R. C. Richards,et al.  Concentrations of epidermal growth factor in mouse milk throughout lactation. , 1983, The Journal of endocrinology.

[11]  E. J. V. van Zoelen,et al.  Ligand-induced Lysosomal Epidermal Growth Factor Receptor (EGFR) Degradation Is Preceded by Proteasome-dependent EGFR De-ubiquitination* , 2003, Journal of Biological Chemistry.

[12]  L. E. Johannessen,et al.  Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies , 2002, The Journal of cell biology.

[13]  N. Normanno,et al.  The ErbB receptors and their ligands in cancer: an overview. , 2005, Current drug targets.

[14]  P. P. Di Fiore,et al.  Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. , 2008, Developmental cell.

[15]  Manuel Hidalgo,et al.  Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  B. Lindeman,et al.  Immunocytochemical Localization of Shc and Activated EGF Receptor in Early Endosomes After EGF Stimulation of HeLa Cells , 2000, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[17]  T. Hayashi,et al.  Radioimmunoassay of human epidermal growth factor--hEGF levels in human body fluids. , 1988, Journal of pharmacobio-dynamics.

[18]  N. Tørring,et al.  Increased expression of heparin binding EGF (HB-EGF), amphiregulin, TGF alpha and epiregulin in androgen-independent prostate cancer cell lines. , 2000, Anticancer research.

[19]  Armando Santoro,et al.  Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. , 2004, The New England journal of medicine.

[20]  Z. Kam,et al.  c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. , 1998, Genes & development.

[21]  P. Gann,et al.  Epidermal growth factor‐related peptides in human prostatic fluid: Sources of variability in assay results , 1997, The Prostate.

[22]  L. Luttrell,et al.  Essential role of c-Cbl in amphiregulin-induced recycling and signaling of the endogenous epidermal growth factor receptor. , 2009, Biochemistry.

[23]  G. Plowman,et al.  Structure and function of human amphiregulin: a member of the epidermal growth factor family. , 1989, Science.

[24]  Neal J Meropol,et al.  Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  S. Decker.  Epidermal growth factor and transforming growth factor-alpha induce differential processing of the epidermal growth factor receptor. , 1990, Biochemical and biophysical research communications.

[26]  Xuejun Jiang,et al.  Grb2 regulates internalization of EGF receptors through clathrin-coated pits. , 2003, Molecular biology of the cell.

[27]  K. Roepstorff,et al.  Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer , 2008, Histochemistry and Cell Biology.

[28]  A. Baron,et al.  Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. , 2008, Biochimica et biophysica acta.

[29]  Rick A. Rogers,et al.  Cbl-mediated Ubiquitinylation Is Required for Lysosomal Sorting of Epidermal Growth Factor Receptor but Is Dispensable for Endocytosis* , 2003, Journal of Biological Chemistry.

[30]  H. Stenmark,et al.  Protein sorting into multivesicular endosomes. , 2003, Current opinion in cell biology.

[31]  Robert J Coffey,et al.  EGF receptor ligands. , 2003, Experimental cell research.

[32]  M. Sliwkowski,et al.  Binding specificities and affinities of egf domains for ErbB receptors , 1999, FEBS letters.

[33]  M. Soley,et al.  Relationship between epidermal growth factor in mouse submandibular glands, plasma, and bile: effects of catecholamines and fasting. , 1994, Endocrinology.

[34]  A. Sorkin,et al.  Recycling of epidermal growth factor-receptor complexes in A431 cells: identification of dual pathways , 1991, The Journal of cell biology.

[35]  Marino Zerial,et al.  Rab proteins as membrane organizers , 2001, Nature Reviews Molecular Cell Biology.

[36]  S. Poulsen,et al.  A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients. , 2001, Cancer research.

[37]  B. Geiger,et al.  Alternative Intracellular Routing of ErbB Receptors May Determine Signaling Potency* , 1998, The Journal of Biological Chemistry.