Signal transduction by MAPK cascade scaffold proteins

在哺乳动物细胞中，仍然不确定不同的丝裂原活化蛋白激酶（MAPK）级联信号传导模块的特异性和效率如何被调节，以及MAPK和可能对生长、存活、分化或细胞死亡起作用的其他类型的信号传导级联之间的串扰如何完成。解决这些问题的关键分子可能是束缚其信号模块的支架蛋白。在此之前，我们分离并鉴定了JSAP 1和JNKBP 1，它们可能作为JNK（MAPK）级联的支架蛋白，通过将级联成员的形成组织成复合物并促进JNK活化。在这项研究中，我们研究了这些支架蛋白如何通过MAPK激酶调节NF-κ B信号。MEKK 1（MAPKKK）过表达到293 T细胞中激活NF-kB，其被JSAP 1或其他JSAP家族成员JSAP 2的共表达抑制。类似地，JNKBP 1的共表达通过MEKK 1或TAK 1（MAPKKK）调节NF-κ B信号传导。此外，我们确定了293 T细胞中支架蛋白与MAPKKKs之间的结合。这些结果表明，支架蛋白JSAP 1/2和JNKBP 1可能通过与MAPKKK相互作用来调节JNK和NF-κ B信号转导。

In mammalian cells, it remains uncertain how the specificity and efficiency of distinct mitogen activated protein kinase (MAPK) cascade signaling modules are regulated, and how a cross-talk between the MAPK and other types of signaling cascade that may play a role on growth, survival, differentiation, or cell death, is done. Key molecules to answer these problems may be scaffold proteins that tether their signaling modules. Previously we isolated and characterized JSAP1 and JNKBP1, which may fuction as scaffold proteins of JNK(MAPK) cascades by organizing the formation of the cascade members into complexes and facilitating JNK activation. In this study, we investigated how these scaffold proteins regulate NF-kB signaling by MAPK kinase kinases. Overexpression of MEKK1 (MAPKKK) into 293T cells activated NF-kB, which was repressed by coexpression of JSAP1 or the other JSAP family member JSAP2. Similarly coexpression of JNKBP1 regulated NF-kB signaling by MEKK1 or TAK1 (MAPKKK). Furthermore, we ascertained the binding between the scaffold proteins and MAPKKKs in 293T cells. These results suggest that the scaffold proteins JSAP1/2 and JNKBP1 may regulate both JNK and NF-kB signaling by interacting with MAPKKKs.