Characteristics of the miR-181 family. (A) Mature sequences of murine miR-181a, b, c, and d. Seed sequences are marked in yellow, asterisks indicate the consensus bases of all four microRNAs. Colored boxes highlight differences between family members. (B) Dynamic expression profiles of miR-181a(/b-1) in T cells from thymus (left) and periphery (right). The shaded area in the thymus indicates the phase of thymic selection. (C) Schematic depiction of miR-181a targets in the TCR signaling cascade. Positive and negative signaling relationships are indicated by solid lines. miR-181a targets PTPN22, DUSP5/6, and SHP-2, which, in turn, regulate Lck and ZAP-70, Erk1/2 and negative costimulatory signals elicited by CTLA4, respectively. Additionally, an indirect effect of miR-181a on SHP-1 has been proposed (denoted by question mark and dotted arrow).