Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the up-regulation of TCR-Driven IL-2 transcription requires SLP-76 binding to EYE at Tyr(595) and Tyr(651)
Lp. Geng et al., Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the up-regulation of TCR-Driven IL-2 transcription requires SLP-76 binding to EYE at Tyr(595) and Tyr(651), J IMMUNOL, 163(11), 1999, pp. 5753-5757
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 hem
opoietic cell-specific adaptor proteins downstream of TCR-activated protein
ty, rosine kinases, SLP-76 has been implicated as an essential component i
n T cell signaling. FYB is selectively phosphorylated by FYN-T, providing a
template for the recruitment of FYN-T and SLP-76 SH2 domains. Coexpression
of FYN-T, FYB, and SLP-76 can synergistically up-regulate IL-2 production
in T cells upon TCR ligation, In this report, we show that two tyrosines, T
yr(595) and Tyr(651), Of FYB are major sites of phosphorylation by FYN-T an
d mediate binding to SLP-76 in jurkat T cells. Furthermore, the synergistic
up-regulation of IL-2 promoter activity in the FYN-T-FYB-SLP-76 pathway is
contingent upon the interaction between FYB and SLP-76, but not the intera
ction between FYB and FYN-T, These observations define a pathway by which S
LP-76 interacts with downstream components in the up-regulation of T cell c
ytokine production.