Immunity
Volume 28, Issue 2, 15 February 2008, Pages 183-196
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Article
Structurally Distinct Phosphatases CD45 and CD148 Both Regulate B Cell and Macrophage Immunoreceptor Signaling

https://doi.org/10.1016/j.immuni.2007.11.024Get rights and content
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Summary

The receptor-type protein tyrosine phosphatase (RPTP) CD148 is thought to have an inhibitory function in signaling and proliferation in nonhematopoietic cells. However, its role in the immune system has not been thoroughly studied. Our analysis of CD148 loss-of-function mice showed that CD148 has a positive regulatory function in B cells and macrophages, similar to the role of CD45 as a positive regulator of Src family kinases (SFKs). Analysis of CD148 and CD45 doubly deficient B cells and macrophages revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SFKs accompanied by substantial alterations in B and myeloid lineage development and defective immunoreceptor signaling. Because these findings suggest the C-terminal tyrosine of SFKs is a common substrate for both CD148 and CD45 phosphatases and imply a level of redundancy not previously appreciated, a reassessment of the function of CD45 in the B and myeloid lineages based on prior data from the CD45-deficient mouse is warranted.

CELLIMMUNO
MOLIMMUNO

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2

These authors contributed equally to this work.

3

Present address: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, 14220, Czech Republic.

4

Present address: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA.