Here we show that while FAK was not required for IGF-IR-dependent signaling and motility of invasive urothelial carcinoma cells, the FAK-related Pyk2 [19], [20] was strongly activated by IGF-I in urothelial carcinoma cells, was critical for IGF-IR-dependent motility and invasion and regulated IGF-I-dependent activation of the Akt and MAPK pathways. The gene discussed is PTK2; the disease is urothelial carcinoma.