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Updated: Aug 30, 2026

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
Dynamic regulation of Src-family kinases by CD45 in B cells
Punya Shrivastava1, Tatsuo Katagiri, Mami Ogimoto
1Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan.
Abstract:
CD45 is a key protein tyrosine phosphatase regulating Src-family protein tyrosine kinases (Src-PTKs) in lymphocytes; precisely how it exerts its effect remains controversial, however. We previously demonstrated that CD45 negatively regulates Lyn in the WEHI-231 B-cell line. Here we show that negative regulation by CD45 is physiologically significant in B cells and that some CD45 is constitutively associated with glycolipid-enriched microdomains (GEMs), where it inhibits Src-PTKs by dephosphorylating both the negative and the positive regulatory sites. Upon B-cell receptor (BCR) ligation, however, CD45 dissociates from GEMs within 30 seconds, inducing phosphorylation of 2 regulatory sites and activation of Src-PTKs, but subsequently reassociates with the GEMs within 15 minutes. Disruption of GEMs with methyl-beta-cyclodextrin results in abrogation of BCR-induced apoptosis in WEHI-231 cells, suggesting GEMs are critical to signals leading to the fate determination. We propose that the primary function of CD45 is inhibition of Src-PTKs and that the level of Src-PTK activation and the B-cell fate are determined in part by dynamic behavior of CD45 with respect to GEMs.
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