Protein tyrosine phosphatase 1C negatively regulates antigen receptor signaling in B lymphocytes and determines thresholds for negative selection

CD45-AP specifically associates with CD45, a protein tyrosine phosphatase essential for lymphocyte differentiation and antigen receptor–mediated signal transduction. CD45 is thought to mediate antigen receptor signaling by dephosphorylating regulatory tyrosine residues on Src family protein tyrosine kinases such as Lck. However, the mechanism for regulating CD45 protein tyrosine phosphatase activity remains unclear. CD45-AP–null mice were created to examine the role of CD45-AP in CD45-mediated signal transduction. T and B lymphocytes showed reduced proliferation in response to antigen receptor stimulation. Both mixed leukocyte reaction and cytotoxic T lymphocyte functions of T cells were also markedly decreased in CD45-AP–null mice. Interestingly, the interaction between CD45 and Lck was significantly reduced in CD45-AP–null T cells, indicating that CD45-AP directly or indirectly mediates the interaction of CD45 with Lck. Our data indicate that CD45-AP is required for normal antigen receptor signaling and function in lymphocytes.

Download Full-text

Cytoskeletal protein tyrosine phosphatase PTPH1 reduces T cell antigen receptor signaling

European Journal of Immunology ◽

10.1002/(sici)1521-4141(200005)30:5<1318::aid-immu1318>3.0.co;2-g ◽

2000 ◽

Vol 30 (5) ◽

pp. 1318-1325 ◽

Cited By ~ 34

Author(s):

Shulin Han ◽

Scott Williams ◽

Tomas Mustelin

Keyword(s):

T Cell ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Antigen Receptor ◽

Cytoskeletal Protein ◽

Receptor Signaling ◽

T Cell Antigen Receptor ◽

Cell Antigen Receptor ◽

Cell Antigen ◽

Antigen Receptor Signaling

Download Full-text

Faculty Opinions recommendation of Aging-related attenuation of EGF receptor signaling is mediated in part by increased protein tyrosine phosphatase activity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1008459.197104 ◽

2003 ◽

Author(s):

Paola Chiarugi

Keyword(s):

Phosphatase Activity ◽

Protein Tyrosine Phosphatase ◽

Egf Receptor ◽

Tyrosine Phosphatase ◽

Receptor Signaling ◽

Protein Tyrosine

Download Full-text

Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells

Journal of Experimental Medicine ◽

10.1084/jem.191.8.1443 ◽

2000 ◽

Vol 191 (8) ◽

pp. 1443-1448 ◽

Cited By ~ 69

Author(s):

Bennett C. Weintraub ◽

Jesse Eunsuk Jun ◽

Anthony C. Bishop ◽

Kevan M. Shokat ◽

Matthew L. Thomas ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

B Lymphocytes ◽

Tyrosine Phosphatase ◽

Antigen Receptor ◽

Cell Receptor ◽

Calcium Flux ◽

Homogeneous Population ◽

Kinase Activation ◽

Antigen Receptor Signaling

Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling in autoreactive B cells, a transgenic model was used to isolate a homogeneous population of tolerant B lymphocytes. These cells were compared with a similar population of naive B lymphocytes. We show that the BCR from naive B cells enters a detergent-insoluble domain of the cell within 6 s after antigen binding, before a detectable increase in BCR phosphorylation. This fraction appears to be important for signaling because it is enriched for lyn kinase but lacks CD45 tyrosine phosphatase and because the BCR that moves into this domain becomes more highly phosphorylated. Partitioning of the BCR into this fraction is unaffected by src family kinase inhibition. Tolerant B cells do not efficiently partition the BCR into the detergent-insoluble domain, providing an explanation for their reduced tyrosine kinase activation and calcium flux in response to antigen. These results identify an early, regulated step in antigen receptor signaling and self-tolerance.

Download Full-text