Regulation of the association between PSTPIP and CD2 in murine T cells.
Prominent in T cells and natural killer cells, CD2 binding protein 1 (CD2BP1) plays an important role in CD2-mediated adhesion and signal transduction. In the current study, we investigated CD2 and PSTPIP (proline, serine, threonine phosphatase interacting protein, murine homologue of CD2BP1) interactions in purified mouse splenic T cells. PSTPIP associated with CD2 in both resting and activated T cells. Following various stimuli, such as concanavalin A, anti-TCRbeta, anti-CD3epsilon, anti-CD3epsilon/phorbol myristate acetate (PMA), IL-2, or PMA/ionomycin, PSTPIP and CD2 expression, as well as their association, increased in a time-dependent fashion. While PSTPIP expression and CD2 expression were comparable across most groups, the PSTPIP-CD2 association stimulated by anti-CD3epsilon alone was significantly greater than with other stimuli. Stimulation by anti-CD3epsilon plus anti-CD28 induced even greater PSTPIP-CD2 association than anti-CD3epsilon treatment alone, indicating that CD28 initiated signals are involved in regulating this interaction. There was no direct association between CD3epsilon or CD28 and PSTPIP. Tyrosine phosphorylated PSTPIP bound poorly to CD2 compared to dephosphorylated PSTPIP, and protein tyrosine phosphatase was shown to affect both phosphorylation of PSTPIP and the CD2-PSTPIP association. In addition to CD2, PSTPIP associated with CD4, CD8, CD54, and CD62L. CD2 and CD4 ligation reciprocally regulated their association with PSTPIP. These findings indicate that T cell activation, particularly through the CD3 and CD28 signal transduction pathways, regulates PSTPIP-CD2 interactions. PSTPIP likely has additional broader effects through interactions with CD4, CD8, CD54, and CD62L, and this may influence T cell responses to antigen.
Bai
Y
Y
Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Ding
Y
Y
Spencer
S
S
Lasky
L A
LA
Bromberg
J S
JS
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D018801:CD2 Antigens / Q000378:metabolism*; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010766:Phosphorylation; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C110097:Pstpip1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D017027:Protein Tyrosine Phosphatases