Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling.
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.
Zhu
Jing W
JW
Departments of Medicine and of Microbiology and Immunology, Howard Hughes Medical Institute, Rosalind Russell Medical Research Center for Arthritis, University of California-San Francisco, San Francisco, CA 94143, USA.
Brdicka
Tomas
T
Katsumoto
Tamiko R
TR
Lin
Joseph
J
Weiss
Arthur
A
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003433:Crosses, Genetic; D016207:Cytokines / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010587:Phagocytosis; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D016207:Cytokines; D011947:Receptors, Antigen, B-Cell; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3