In agreement, among proteins possessing PIP3-binding PH domains, Btk and Gab1 inhibit Akt whereas Grp1 and ARNO do not.40 Our data demonstrate that RanBP9/TSSC3 complex inhibits the activity of Src and its downstream effectors (PIPs, Akt) by associating with Src, suggesting that RanBP9/TSSC3 complex, at least in osteosarcoma, affects signals upstream of Akt but does not repress Akt activity by competitively binding PIPs. The gene discussed is GAB1; the disease is osteosarcoma.