Phosphorylation of the N-terminal and C-terminal CD3-epsilon-ITAM tyrosines is differentially regulated in T cells |
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Authors: | Guirado María de Aós Isabel Orta Teresa Rivas Luis Terhorst Cox Zubiaur Mercedes Sancho Jaime |
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Affiliation: | Instituto de Parasitología y Biomedicina, Consejo Superior de Investigaciones Científicas, Granada, 18001, Spain. |
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Abstract: | Tyrosine phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) within CD3 chains is crucial for the recruitment of protein tyrosine kinases and effector molecules into the T cell receptor. Thus, phenylalanine substitution at the N-terminal tyrosine residue of the CD3-epsilon-ITAM abolished signal transduction functions of this ITAM, including phosphorylation at the C-terminal ITAM tyrosine, and its association with ZAP-70. In contrast, mutation at the C-terminal tyrosine of CD3-epsilon-ITAM did not prevent phosphorylation at the N-terminal tyrosine, nor its association with Lck, or p85 PI 3-K regulatory subunit. In contrast to the ZAP-70/diphosphorylated CD8-epsilon-ITAM interaction, the Lck/monophosphorylated CD8-epsilon-ITAM interaction was sensitive to octylglucoside, an agent that disrupts Lck interaction with membrane rafts. Therefore, association of Lck with membrane rafts seems to be essential for stabilization of Lck/CD3-epsilon protein-protein interactions. Overall, the data suggest that the sequential and coordinated phosphorylation of CD3-epsilon-ITAM tyrosines provides to CD3-epsilon the potential to interact with multiple downstream effectors and signaling pathways. |
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Keywords: | T lymphocytes signal transduction T cell receptor protein tyrosine kinases/phosphatases second messengers |
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