Figure 5.

Itpkb controls immune cell biology by dampening store-operated Ca²⁺ entry (SOCE). Several studies suggest that in peripheral T cells, developing and mature B cells, neutrophils and macrophages, Itpkb or Itpkc dampen SOCE through Orai channels (23, 39–42, 44, 59). This may be required for T cell viability, for preventing B cell anergy, and for ensuring neutrophil function. The ability of an exogenously provided cell-permeable IP₄-ester to reduce SOCE very quickly after administration would be consistent with direct SOCE inhibition through IP₄ (39, 59). However, variably affected ER store release and previously published, complicated roles for Itpks, IP₃, IP₄, and IP₄ metabolites in controlling Ca²⁺ mobilization in mammalian cells could point to alternate mechanisms and possible other effectors (8, 45, 60, 61). For more detailed discussions, see text.