| 背景资料 | The c-Jun N-terminal Kinases (JNKs) are part of the MAPK (mitogen-activated protein kinase) system that transmits signals from the extracellular milieu to both the cytoplasm and nucleus of the cell. Following perturbation at the cell membrane, MEKKs/MAP3Ks are initially activated, followed by their activation of MKKs/MAP2Ks, and MKKs activation of MAPKs/MAP(1)Ks. There are three classes of MAPKs: ERKs, p38 Kinases and JNKs. JNKs are 45-55 kDa protein products of three genes which, through alternative splicing, generate up to 10 possible isoforms. The phosphorylation targets for MAPKs vary, but include p53, c-MYC, ATF2 and c-Jun, the latter molecule representing the namesake for the enzyme group. The three human JNKs share approximately 80% aa sequence identity. JNKs from human, mouse and rat all contain a conserved Met-Met-Thr(183)-Pro-Tyr(185)-Val-Val motif that undergoes dual phosphorylation by MMK4 and MMK7 to activate the different JNKs. Activated by environmental stresses and inflammatory cytokines, JNKs translocate to the nucleus where they regulate the activity of several transcription factors; including the c-Jun component of AP-1 and ATF-2. |
