Summary of the transmembrane adaptor molecules investigated in this study as previously described4
Molecule . | . | . | . | |
|---|---|---|---|---|
| Acronym . | Full name and key reference . | MW, kDa . | Molecular features* . | |
| LAT | Linker for activation of T cells5,6 | 36-38 | Essential, after antigen binding to TCR, for initiation of T-cell signaling cascades that lead to production of interleukin 2. Disruption causes a maturation block in early thymocytes. Also involved in NK-cell signaling and platelet activation. | |
| NTAL (LAB) | Non–T-cell activation linker7,8 | 30 | Initially thought to be the B-cell equivalent of LAT,9 but now shown to be a negative regulator of early stages of BCR signaling.10 Appears also to be a negative regulator of FcϵRl signaling in mast cells.11,12 | |
| PAG (Cbp) | Protein associated with glycosphingo-lipid-enriched microdomains13,14 | 68-85 | Phosphorylated in resting T cells, thereby recruiting Csk kinase, which phosphorylates and thus reversibly inhibits Lck kinase. Dephosphorylation induced after TCR ligation releases Csk and contributes to Lck activation. Also implicated in regulation of BCR and FcϵRl signaling. | |
| LIME | Lck-interacting membrane protein15,16 | 31 | Resembles PAG in its ability to bind Csk but also binds and thereby activates Src kinases (eg, Lck) directly. Major target of phosphorylation after CD4 ligation. | |
| TRIM | TCR-interacting molecule17 | 30 | Cysteine-linked homodimer. Potentially involved in the negative regulation of TCR-mediated signals. | |
| SIT | SH2 domain–containing protein tyrosine phosphatase–interacting transmembrane adaptor protein18 | 30-40 | Cysteine-linked homodimer, with an N-glycosylated extracellular domain. Phosphorylated after antigen binding to TCR and (like PAG and LIME) can bind Csk. Probably involved in the negative regulation of TCR-mediated signaling. | |
| LAX | Linker for activation of X cells19 | 70 | Phosphorylated after antigen binding to TCR, but its physiologic role remains to be clarified. Probably acts as a negative regulator. | |
Molecule . | . | . | . | |
|---|---|---|---|---|
| Acronym . | Full name and key reference . | MW, kDa . | Molecular features* . | |
| LAT | Linker for activation of T cells5,6 | 36-38 | Essential, after antigen binding to TCR, for initiation of T-cell signaling cascades that lead to production of interleukin 2. Disruption causes a maturation block in early thymocytes. Also involved in NK-cell signaling and platelet activation. | |
| NTAL (LAB) | Non–T-cell activation linker7,8 | 30 | Initially thought to be the B-cell equivalent of LAT,9 but now shown to be a negative regulator of early stages of BCR signaling.10 Appears also to be a negative regulator of FcϵRl signaling in mast cells.11,12 | |
| PAG (Cbp) | Protein associated with glycosphingo-lipid-enriched microdomains13,14 | 68-85 | Phosphorylated in resting T cells, thereby recruiting Csk kinase, which phosphorylates and thus reversibly inhibits Lck kinase. Dephosphorylation induced after TCR ligation releases Csk and contributes to Lck activation. Also implicated in regulation of BCR and FcϵRl signaling. | |
| LIME | Lck-interacting membrane protein15,16 | 31 | Resembles PAG in its ability to bind Csk but also binds and thereby activates Src kinases (eg, Lck) directly. Major target of phosphorylation after CD4 ligation. | |
| TRIM | TCR-interacting molecule17 | 30 | Cysteine-linked homodimer. Potentially involved in the negative regulation of TCR-mediated signals. | |
| SIT | SH2 domain–containing protein tyrosine phosphatase–interacting transmembrane adaptor protein18 | 30-40 | Cysteine-linked homodimer, with an N-glycosylated extracellular domain. Phosphorylated after antigen binding to TCR and (like PAG and LIME) can bind Csk. Probably involved in the negative regulation of TCR-mediated signaling. | |
| LAX | Linker for activation of X cells19 | 70 | Phosphorylated after antigen binding to TCR, but its physiologic role remains to be clarified. Probably acts as a negative regulator. | |
LAT, NTAL, PAG, and LIME are associated with lipid rafts; TRIM, SIT, and LAX are not associated with lipid rafts.
MW indicates molecular weight.
See Figure 1 for additional descriptions of molecular features