T-Cell-Specific Deletion of Map3k1 Reveals the Critical Role for Mekk1 and Jnks in Cdkn1b-Dependent Proliferative Expansion.

MAPK signaling is important for T lymphocyte development, homeostasis, and effector responses. To better understand the role of Mekk1 (encoded by Map3k1) in T cells, we conditionally deleted Map3k1 in Lck(Cre/+)Map3k1(f/f) mice, and these display larger iNKT cell populations within the liver, spleen, and bone marrow. Mekk1 signaling controls splenic and liver iNKT cell expansion in response to glycolipid antigen.

The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines.

Unlike the other MAP3Ks, MEKK1 (encoded by Map3k1) contains a PHD motif. To understand the role of this motif, we have created a knockin mutant of mouse Map3k1 (Map3k1(m) (PHD)) with an inactive PHD motif. Map3k1(m) (PHD) ES cells demonstrate that the MEKK1 PHD controls p38 and JNK activation during TGF-β, EGF and microtubule disruption signalling, but does not affect MAPK responses to hyperosmotic stress.

siRNA high-throughput kinase library screen identifies protein kinase, DNA-activated catalytic polypeptide to play a role in MyD88-induced IFNA2 activation and IL-8 secretion.

The discovery of RNA interference has led to the development of short interfering RNA (siRNA) screening, which has been widely used to study biological pathways. Here, we describe the development and validation of a system suitable to identify cellular genes involved in interferon A2 (IFNA2) promoter activation and interleukin (IL)-8 secretion downstream of MyD88. Forty genes were identified.