CD45: A Critical Regulator of Signaling Thresholds in Immune Cells

Abstract

Regulation of tyrosine phosphorylation is a critical control point for integration of environmental signals into cellular responses. This regulation is mediated by the reciprocal actions of protein tyrosine kinases and phosphatases. CD45, the first and prototypic receptor-like protein tyrosine phosphatase, is expressed on all nucleated hematopoietic cells and plays a central role in this process. Studies of CD45 mutant cell lines, CD45-deficient mice, and CD45-deficient humans initially demonstrated the essential role of CD45 in antigen receptor signal transduction and lymphocyte development. It is now known that CD45 also modulates signals emanating from integrin and cytokine receptors. Recent work has focused on regulation of CD45 expression and alternative splicing, isoform-specific differences in signal transduction, and regulation of phosphatase activity. From these studies, a model is emerging in which CD45 affects cellular responses by controlling the relative threshold of sensitivity to external stimuli. Perturbation of this function may contribute to autoimmunity, immunodeficiency, and malignancy. Moreover, recent advances suggest that modulation of CD45 function can have therapeutic benefit in many disease states.

Flow cytometry APC‐tandem dyes are degraded through a cell‐dependent mechanism

“…S1). Panleukocyte anti-CD45 antibodies were coupled to APC-tandem dyes labeled lymphocytes, monocytes, and polymorphonuclear leukocytes (19) (Figs. 1A and 1B, left panels).…”

CD45 isoform expression is associated with different susceptibilities of human naive and effector CD4+ T cells to respond to IL‐4

“…Cross-linking CD45 may favor dimerization and thus reduces PTPase activity predominantly in CD45R0 + T cells [29,42], possibly due to the fact that CD45R0 molecules undergo the least extracellular sialylation and O-glycosylation. In fact, PTPase activity of CD45R0 + T cells was reduced to levels almost comparable to CD45RA + T cells following CD45 cross-linking.…”

Altered lipid raft–associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus

“…In contrast, a membrane protein tyrosine phosphatase, CD45, positively regulates Lyn by dephosphorylating Y-507, which causes a conformational change that reveals the catalytic domain of Lyn and promotes autophosphorylation of the positive regulatory tyrosine at position 396 (Y-396) (20,21). This model is supported by studies of CD45 Ϫ/Ϫ B lymphocytes, in which it has been shown that Y-507 in Lyn is hyperphosphorylated and that BCR-mediated signaling is attenuated (22).…”