The cytoplasmic domain of CD98hc regulates integrin-induced signal transduction and spreading. (A) Signaling: CD98hc is a major contributor to integrin-dependent signal transduction involving pFAK, Akt as well as the MEK/ERK pathways. High and low CD98hc Caki2 cells as well as the mutated Caki2 cells silCD98hc/Caki2, trunsilCD98hc/Caki2 and poinsilCD98hc/Caki2 were permitted to adhere to fibronectin for time-spans indicated. Phosphorylation of FAK (lane 1) was compared to total FAK (lane 2) as well as phosphorylation of pSer Akt (lane 3) was compared to total Akt (lane 4). Furthermore, phosphorylation of p44/42 MEK/ERK (lane 5) was compared to total p44/42 (lane 6). Only the trunsilCD98hc Caki2 cells were unable to rescue the lowCD98hc/Caki2 effect on intracellular signal transduction. n = 3, data represent the mean ± SEM, * p < 0.001 (B) Cell spreading assays: highCD98hc/Caki2 and lowCD98hc/Caki2 cells were either transfected with dominant active FAK of the empty control vector. Cells were seeded on fibronectin (FN, 10 μg/ml) for indicated time spans before cell area was assessed. Bars indicate SEM- standard error of mean.