GRAP2 (also called GADS) is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway [, ]. It also has roles in antigen-receptor and tyrosine kinase mediated signaling []. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage []. GRAP2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1) [], the RxxK motif in SLP-76 [, ]and HPK1 [], and the RxxxxK motif in phosphatase-like protein HD-PTP [].
