Journal of Leukocyte Biology eBioscience full spectrum cell analysis
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on September 1, 2008

Published online before print June 17, 2008
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow Supplemental Figures 1 and 2
Right arrow All Versions of this Article:
jlb.0308171v1
84/3/852    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Yu, W.
Right arrow Articles by Stanley, E. R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yu, W.
Right arrow Articles by Stanley, E. R.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0308171

Received for publication March 11, 2008.
Revised April 23, 2008.
Accepted for publication May 1, 2008.

Article

CSF-1 receptor structure/function in MacCsf1r–/– macrophages: regulation of proliferation, differentiation, and morphology

Wenfeng Yu , Jian Chen , Ying Xiong , Fiona J. Pixley , Xu-Ming Dai , Yee-Guide Yeung , and E. Richard Stanley @

Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA

@ To whom correspondence should be addressed. E-mail: rstanley{at}aecom.yu.edu.


  Abstract

CSF-1 is the major regulator of tissue macrophage development and function. A GM-CSF-dependent, CSF-1 receptor (CSF-1R)-deficient F4/80hiMac-1+Gr1–CD11c+ bone marrow macrophage (BMM) line (MacCsf1r-/-) was developed to study the roles of the eight intracellular CSF-1R tyrosines phosphorylated upon receptor activation. Retroviral expression of the wild-type CSF-1R rescued the CSF-1-induced survival, proliferation, differentiation, and morphological characteristics of primary BMM. Mutation of all eight tyrosines failed to rescue, whereas the individual Y -> F mutants (544, 559, 697, 706, 721, 807, 921, 974) rescued these CSF-1-inducible phenotypes to varying degrees. The juxtamembrane domain Y559F and activation loop Y807F mutations severely compromised proliferation and differentiation, whereas Y706, Y721F, and Y974F mutations altered morphological responses, and Y706F increased differentiation. Despite their retention of significant in vitro tyrosine kinase activity, Y559F and Y807F mutants exhibited severely impaired in vivo receptor tyrosine phosphorylation, consistent with the existence of cellular mechanisms inhibiting CSF-1R tyrosine phosphorylation that are relieved by phosphorylation of these two sites. The MacCsf1r-/- macrophage line will facilitate genetic and proteomic approaches to CSF-1R structure/function studies in the major disease-related CSF-1R-expressing cell type.

Key Words: tyrosine kinase • tyrosine phosphorylation • hematopoietic growth factor • receptor tyrosine kinase mutations






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2008 by the Society for Leukocyte Biology.