Only JAK3, out of a panel of four tyrosine kinases, inhibits PLD2 GEF. (A) Effect of tyrosine kinases Src, Fes, EGFR and JAK3 on PLD2 GEF activity in vitro (using recombinant proteins). (B) JAK3 has a negative effect on PLD2-GEF activity, whereas (C) it has a positive effect on lipase in vivo. COS-7 cells were overexpressed with PLD2-WT or PLD2-Y415F in the absence or presence of JAK3. Immunoprecipitated (I.P.) PLD2 from these cells was used for GEF assays (the smaller the bars, the higher the GEF activity). Triplicate results are means±s.e.m. and are expressed in terms of relative [3H]-GDP dissociation. *denotes significant differences (P<0.005) above controls; #denotes significant differences (P<0.005) below controls.