CD45 is a transmembrane tyrosine phosphatase implicated in T cell antigen receptor (TCR)-mediated activation. In T cell variants expressing progressively lower levels of CD45 (from normal to undetectable), CD45 expression was inversely related to spontaneous tyrosine phosphorylation of multiple proteins, including the TCR zeta chain, and was directly correlated with TCR-driven phosphoinositide ...

A widely accepted model for regulation of the Lck tyrosine kinase is that it is activated by CD45-mediated dephosphorylation of its COOH-terminal negative regulatory tyrosine (Tyr505). Previous work from our laboratory, however, found that despite hyperphosphorylation of Tyr505, the activity of Lck from CD45- T cell lines was actually increased due to hyperphosphorylation of the positive regula...

CD45 (the leukocyte common antigen) is known to function as a tyrosine phosphatase in leukocyte signaling. Biochemical studies indicate that CD45 is involved in the regulation both of T cell receptor-associated kinases and Janus kinases that transmit signals from cytokine receptors. However, the function of the different isoforms of CD45 generated by complex alternative splicing, and indeed the...

CD45 is a transmembrane protein-tyrosine phosphatase required for antigen receptor signaling in lymphocytes. CD45 activates the Src family protein-tyrosine kinases, p56lck and p59fyn, by dephosphorylating a negative regulatory tyrosine in the carboxyl terminus. Immunoprecipitation of CD45 precipitates p56lck and CD45AP. Although the function of CD45AP is unknown, it has been proposed to be an a...

The CD45 antigen is present on all cells of the hematopoietic lineage. Using a murine model, we have determined whether a lytic CD45 monoclonal antibody can produce persistent aplasia and whether it could facilitate syngeneic or allogeneic stem cell engraftment. After its systemic administration, we found saturating quantities of the antibody on all cells expressing the CD45 antigen, both in ma...

Transmembrane protein tyrosine phosphatases, such as CD45, can act as both positive and negative regulators of cellular signaling. CD45 positively modulates T cell receptor (TCR) signaling by constitutively priming p56lck through the dephosphorylation of the C-terminal negative regulatory phosphotyrosine site. However, CD45 can also exert negative effects on cellular processes, including events...

Converging lines of evidence indicate dysregulation of the key immunoregulatory molecule CD45 (also known as leukocyte common antigen) in Alzheimer's disease (AD). We report that transgenic mice overproducing amyloid-β peptide (Aβ) but deficient in CD45 (PSAPP/CD45(-/-) mice) faithfully recapitulate AD neuropathology. Specifically, we find increased abundance of cerebral intracellular and extra...

The cytoplasmic tail of CD45 (ct-CD45) is proteolytically cleaved and released upon activation of human phagocytes. It acts on T cells as an inhibitory, cytokine-like factor in vitro. Here, we show that ct-CD45 is abundant in human peripheral blood plasma from healthy adults compared with plasma derived from umbilical cord blood and plasma from patients with rheumatoid arthritis or systemic lup...

A reduction in progenitor cell populations that help preserve vascular continuity and induce vascularization may accentuate endothelial cell apoptosis and dysfunction, ultimately contributing to organ failure and increased cardiovascular disease in chronic kidney disease (CKD). We hypothesized that CD45+ myeloid and CD34+ hematopoietic circulating progenitor cell (CPC) subpopulations would be r...

The chemokine receptor CXCR4 and its cognate ligand, stromal cell-derived factor-1alpha (CXCL12), regulate lymphocyte trafficking and play an important role in host immune surveillance. However, the molecular mechanisms involved in CXCL12-induced and CXCR4-mediated chemotaxis of T-lymphocytes are not completely elucidated. In the present study, we examined the role of the membrane tyrosine phos...