Engagement of FcεRI results in the activation of SphK1 and 2 in both human and murine MC. While SphK1 in human MC mediates degranulation and cytokine production, SphK2 is crucial for these processes in murine MC. SphK1 in human MC regulates chemotaxis towards antigen as demonstrated previously (31), while SphK1 and SphK2 jointly regulate chemotaxis of murine MC. However, the role for SphK1 or SphK2 cannot be generalized to all MC for all mast cell responses, even within the same species, since SphK1 also seems to play a role in cytokine production in BMMC and in the degranulation of PDMC from the SphK1-/- mouse (see results section and discussion), and SphK2 has a role in cytokine production in the immortalized human MC line LAD2. A changed environment (as in the complete absence of SphK1 in the mouse) or changes in the progenitors may alter the functional requirements for these kinases during allergic activation. Dashed lines represent previously reported findings, as indicated.