Reactome | Recruitment of GADS:SLP-76 to p-5Y-LAT

Recruitment of GADS:SLP-76 to p-5Y-LAT

Stable Identifier

R-HSA-2396561

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Gads/GRAP2 (GRB2-related adapter protein 2) is member of the GRB2 adaptor family with a central SH2 domain and linker region flanked by amino- and carboxy-terminal SH3 domains. SLP-76 associates constitutively via its central 20-amino acid proline-rich domain with the C-terminal SH3 domain of Gads, which recruits it to LAT following receptor stimulation. Upon LAT phosphorylation, Gads:SLP-76 complex principally binds to phosphorylated LAT tyrosine 191, with a reduced amount of binding to phosphorylated tyrosine 171 and no interaction with phosphorylated tyrosines 132 or 226 (Houtman et al. 2004, Zhu et al. 2003). Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways (Liu et al. 1999). The LAT-Gads-SLP-76 complex creates a platform for the recruitment of multiple signaling molecules, including PLCgamma1, GRB2, NCK, Rho GEFs, VAV and the Tec-family kinases ITK and BTK (Liu et al. 1999 & 2001, Asada et al. 1999, Yablonski et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
11390650	Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT Yablonski, D, Kadlecek, T, Weiss, A	Mol Cell Biol	2001
10224278	Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT Asada, H, Ishii, N, Sasaki, Y, Endo, K, Kasai, H, Tanaka, N, Takeshita, T, Tsuchiya, S, Konno, T, Sugamura, K	J. Exp. Med.	1999
10021361	The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors Liu, SK, Fang, N, Koretzky, GA, McGlade, CJ	Curr. Biol.	1999