Signals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the αβ T cell lineage. In contrast to the γδ TCR, the pre-TCR localizes cell-autonomously to membrane rafts, where it appears to signal in a constitutive and ligand-independent manner. We addressed here the role played by structural features specific to the cytoplasmic domain of the pre-TCRα chain (pTα). More specifically, we examined a COOH-terminal proline-rich sequence that might play a role in signal transduction and a juxtamembrane cysteine residue that could be a target for palmitoylation, thus allowing spontaneous raft localization. Expression of pTα mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pTα cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pTα juxtamembrane cysteine appeared to be dispensable for pre-TCR function.
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Supported by the NIH (grants A147281 and A145846 to H. v. B.), a “Eugenia Spanopoulou” – Irvington Institute grant (to I. A.) and a National Science Foundation grant (to C. B.). We thank B. Reizis for LR2 cell line and R. Mulligan for the MMLV-based retroviral vector; M. Prakriya and L. Scorrano for their advice and help with the Ca2+ measurements; S. Hoeflinger for technical assistance; H. Levine and M. Cantley for cell sorting; and E. Smith for help with preparation of the manuscript.
The authors declare no competing financial interests.
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