These results, together with our observation that Erk blockage resulted in a significant inhibition of SphK1/2 activation induced by FSH, suggest that Erk could be placed both upstream and downstream of the SphK1/2 signaling and has a dual role in the initiation and amplification of the SphK1/2 signaling loop in ovarian cancer cells. The gene discussed is SPHK1; the disease is ovarian cancer.