|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 32, 28830-28835, August 9, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Hart and Louis Laboratory, Division of Clinical
Immunology, Department of Medicine, UCLA School of Medicine, Los
Angeles, California 90095-1680
CD45 plays a critical regulatory role in receptor
signaling through its protein tyrosine phosphatase and Janus kinase
(JAK) phosphatase activities. To investigate whether CD45 also plays a
regulatory role in Ig class switching in human B cells, we examined the
effects of CD45 triggering on Ig class switching to IgE and its
relationship with CD45 JAK phosphatase activity. Anti-CD45 triggering
of CD45 significantly inhibited interleukin-4 + anti-CD40-induced switch recombination in a switch recombination vector
assay in stably transfected Ramos 2G6 human B cells, as well as Ig
CD45 Controls Interleukin-4-mediated IgE Class Switch
Recombination in Human B Cells through Its Function as a
Janus Kinase Phosphatase*
germ-line transcription and Sµ-S switch recombination in primary
human B cells. These negative regulatory effects on Ig class switching were concomitant with the ability of CD45 to dephosphorylate the induced phosphorylation of JAK1, JAK3, and signal transducer and activator of transcription 6, but not on
stress-activated/mitogen-activated protein kinases. We also showed that
phosphorylated JAK1 and JAK3 were directly dephosphorylated by
recombinant CD45 in vitro. These results indicate
that CD45 is able to function as JAK phosphatase in human B cells and
that this activity is directly associated with the negative regulation
of the class switch recombination to IgE. CD45 may be an appropriate
target drug for modulating IgE in allergic diseases.
*
This work was supported by National Institutes of Health
Grants AI-40551, AI-34567, AI-15251, AI-28697, and CA-16042 and an award from the Stein-Oppenheimer Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Division of Clinical
Immunology/Allergy, Dept. of Medicine, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-1680. Tel.: 310-825-3699; Fax:
310-206-8107; E-mail: kzhang@mednet.ucla.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Doi, K. Obayashi, T. Kadowaki, H. Fujii, and S. Koyasu PI3K is a negative regulator of IgE production Int. Immunol., April 1, 2008; 20(4): 499 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Obayashi, T. Doi, and S. Koyasu Dendritic cells suppress IgE production in B cells Int. Immunol., February 1, 2007; 19(2): 217 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I K Lund, J A Hansen, H S Andersen, N P H Moller, and N Billestrup Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling J. Mol. Endocrinol., April 1, 2005; 34(2): 339 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. Fleming, C. D. Milne, and C. J. Paige CD45-Deficient Mice Accumulate Pro-B Cells Both In Vivo and In Vitro J. Immunol., August 15, 2004; 173(4): 2542 - 2551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bhaduri and R. Sowdhamini A genome-wide survey of human tyrosine phosphatases Protein Eng. Des. Sel., December 1, 2003; 16(12): 881 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yamada, D. Zhu, K. Zhang, and A. Saxon Inhibition of Interleukin-4-induced Class Switch Recombination by a Human Immunoglobulin Fc{gamma}-Fc{epsilon} Chimeric Protein J. Biol. Chem., August 29, 2003; 278(35): 32818 - 32824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Zhang Accessibility control and machinery of immunoglobulin class switch recombination J. Leukoc. Biol., March 1, 2003; 73(3): 323 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhou, A. Saxon, and K. Zhang Human Activation-Induced Cytidine Deaminase Is Induced by IL-4 and Negatively Regulated by CD45: Implication of CD45 as a Janus Kinase Phosphatase in Antibody Diversification J. Immunol., February 15, 2003; 170(4): 1887 - 1893. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |