PMID: 9428788Jan 15, 1998Paper

Identification of p185neu sequences required for monoclonal antibody- or ligand-mediated receptor signal attenuation

DNA and Cell Biology
X QianM I Greene

Abstract

Anti-p185neu antibodies downmodulate constitutively active p185neu receptors from the cell surface, which is associated with a reduction in the transformed phenotype. We have analyzed a group of mutant p185neu forms with carboxyl (C)-terminal truncations and/or an internal deletion of amino acids 1008-1057. Receptor endocytosis and degradation were examined by flow cytometric analysis and pulse-chase assays following anti-p185neu monoclonal antibody (MAb) treatment. Deletion of a sequence within the distal carboxyl terminus, including three known autophosphorylation sites, did not affect MAb-mediated receptor surface downmodulation and degradation of surface receptor. However, kinase-active deletion mutants with elimination of the putative internalization sequence (Tint delta), or Tint delta mutants also containing a large C-terminal truncation, displayed markedly impaired receptor endocytosis in response to MAb treatment. Cells expressing endocytosis-defective mutant proteins became insensitive to anti-p185neu MAb-mediated inhibition of anchorage-independent growth and were more oncogenic in vivo. Cells expressing endocytosis-defective mutant EGFR/neu chimeric proteins were more transforming upon EGF addition when compared to ...Continue Reading

References

Sep 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·R M Pruss, H R Herschman
Feb 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·X L QuianM I Greene
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P CarterH M Shepard
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·Y MikamiM I Greene
Dec 18, 1991·European Journal of Biochemistry·E Smythe, G Warren
Jan 11, 1991·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·T M WilliamsH C Maguire
Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J A DrebinM I Greene
Aug 1, 1994·Molecular and Cellular Biology·A G BatzerJ Schlessinger
Sep 12, 1995·Proceedings of the National Academy of Sciences of the United States of America·A NesterovG N Gill
Nov 1, 1994·The Journal of Cell Biology·H DamkeS L Schmid
Jul 30, 1993·Science·A Sorkin, G Carpenter
Jun 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A Sorkin, C M Waters
Mar 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J BaselgaL Norton

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Citations

Dec 31, 2003·Molecular and Cellular Neurosciences·John A BoockvarDonald M O'Rourke
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·B W ParkM I Greene
Feb 2, 2010·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Miriam ColomboPaolo Verderio
May 20, 2009·Experimental and Molecular Pathology·Jaclyn A FreudenbergMark I Greene

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