HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Layton, J. E. Articles by Nice, E. C. Search for Related Content PubMed PubMed Citation Articles by Layton, J. E. Articles by Nice, E. C. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 266, Issue 35, 23815-23823, 12, 1991

Identification of a functional domain of human granulocyte colony- stimulating factor using neutralizing monoclonal antibodies

JE Layton, G Morstyn, LJ Fabri, GE Reid, AW Burgess, RJ Simpson and EC Nice
Melbourne Tumour Biology Branch, Ludwig Institute for Cancer Research, Australia.

Human granulocyte colony-stimulating factor (G-CSF) is a hemopoietic growth factor that is being used successfully to treat various forms of neutropenia. To define functionally important regions of G-CSF, we have prepared 37 monoclonal anti-G-CSF antibodies and mapped the regions of G-CSF recognized by different antibody groups. Antibodies recognizing similar epitopes were identified by competition assays, neutralization assays, conformation dependence and cross-reactivity with canine G-CSF. Seven of eight neutralizing antibodies fell into two related epitope groups and were conformation-dependent. The eighth was unrelated and conformation-independent. Peptides of G-CSF were generated by chemical or enzymatic digestion and tested for antibody reactivity. One of the neutralizing antibodies (LMM351) recognized a small, disulfide-bonded peptide from the V8 protease digest (residues 34-46). A synthetic peptide (residues 20-58) was recognized by all the neutralizing antibodies, implicating this disulfide-bonded loop in receptor binding. The epitopes recognized by nonneutralizing antibodies were found throughout G-CSF. Thus, regions of G-CSF that are not involved in receptor binding have also been defined. A CNBr peptide (residues 1- 121) had greatly reduced biological activity, indicating that the COOH terminus is required for receptor binding. We predict that residues 20- 46 and the COOH terminus bind to the G-CSF receptor.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Hammacher, R. T. Richardson, J. E. Layton, D. K. Smith, L. J. L. Angus, D. J. Hilton, N. A. Nicola, J. Wijdenes, and R. J. Simpson The Immunoglobulin-like Module of gp130 Is Required for Signaling by Interleukin-6, but Not by Leukemia Inhibitory Factor J. Biol. Chem., August 28, 1998; 273(35): 22701 - 22707. [Abstract] [Full Text] [PDF]

				J. E. Layton, N. E. Hall, F. Connell, J. Venhorst, and H. R. Treutlein Identification of Ligand-binding Site III on the Immunoglobulin-like Domain of the Granulocyte Colony-stimulating Factor Receptor J. Biol. Chem., September 21, 2001; 276(39): 36779 - 36787. [Abstract] [Full Text] [PDF]