Allelic Exclusion of the T Cell Receptor b Locus Requires the SH 2 Domain – containing Leukocyte Protein ( SLP ) - 76 Adaptor Protein
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چکیده
Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4 2 CD8 2 double-negative (DN) thymocytes into CD4 1 CD8 1 double-positive (DP) cells and for TCRb allelic exclusion. The adaptor protein SH2 domain–containing leukocyte protein (SLP)-76 has been shown to play a crucial role in thymic development, because thymocytes of SLP-76 2 / 2 mice are arrested at the CD25 1 CD44 2 DN stage. Here we show that SLP-76 2 / 2 DN thymocytes express the pre-TCR on their surfaces and that introduction of a TCRa/b transgene into the SLP-76 2 / 2 background fails to cause expansion of DN thymocytes or developmental progression to the DP stage. Moreover, analysis of TCRb rearrangement in SLP-76 2 / 2 TCR-transgenic mice or in single CD25 1 CD44 2 DN cells from SLP-76 2 / 2
منابع مشابه
Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4(-)CD8(-) double-negative (DN) thymocytes into CD4(+)CD8(+) double-positive (DP) cells and for TCR-beta allelic exclusion. The adaptor protein SH2 domain-containing leukocyte protein (SLP)-76 has been shown to play a crucial role in thymic development, because thymocytes of SLP-76(-/-) m...
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SLP-76 (Src homology (SH) 2-domain-containing leukocyte protein of 76 kDa) and FYB/SLAP (FYN-T-binding protein/SLP-76-associated protein) are two hemopoietic cell-specific adaptor proteins downstream of TCR-activated protein tyrosine kinases. SLP-76 has been implicated as an essential component in T cell signaling. FYB is selectively phosphorylated by FYN-T, providing a template for the recruit...
متن کاملAdapter proteins SLP-76 and BLNK both are expressed by murine macrophages and are linked to signaling via Fcgamma receptors I and II/III.
The SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kDa) adapter protein is expressed in T cells and myeloid cells, whereas its homologue BLNK (B cell linker protein) is expressed in B cells. SLP-76 and BLNK link immunoreceptor tyrosine-based activation motif-containing receptors to signaling molecules that include phospholipase C-gamma, mitogen-activated protein kinases, and t...
متن کاملInvolvement of Lat, Gads, and Grb2 in Compartmentation of Slp-76 to the Plasma Membrane
B cell linker protein (BLNK) and Src homology 2 domain-containing leukocyte protein of 76 kD (SLP-76) are adaptor proteins required for B cell receptor (BCR) and T cell receptor function, respectively. Here, we show that expression of SLP-76 cannot reconstitute BCR function in Zap-70(+)BLNK(-) B cells. This could be attributable to inability of SLP-76 to be recruited into glycolipid-enriched mi...
متن کاملThe hematopoietic-specific adaptor protein Gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors
BACKGROUND The adaptor protein Gads is a Grb2-related protein originally identified on the basis of its interaction with the tyrosine-phosphorylated form of the docking protein Shc. Gads protein expression is restricted to hematopoietic tissues and cell lines. Gads contains a Src homology 2 (SH2) domain, which has previously been shown to have a similar binding specificity to that of Grb2. Gads...
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