Proteins like Raf kinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions...Proteins like Raf kinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions, have been demon- strated to play an increasingly important role in a number of cell types and organisms. These proteins have been implicated in development as well as the progression of cancer. RKIP is a particularly interesting regulator, as it is a highly conserved, ubiquitously expressed protein that has been shown to play a role in growth and differentiation in a number of organisms and can regulate multiple signaling pathways. RKIP is also the first MAP kinase signaling modulator to be identified as playing a role in cancer metastasis, and identification of the mechanism by which it regulates Raf-1 activation provides new targets for therapeutic intervention.展开更多
Protein kinase CK2 consists of two catalytic subunits (CK2α) and two regulatory subunits (CK2β). Here, we report the crystal structures of rat CK2α mutant (rCK2α-△C, 1—335) and CK2β (rCK2β). The overall topolo...Protein kinase CK2 consists of two catalytic subunits (CK2α) and two regulatory subunits (CK2β). Here, we report the crystal structures of rat CK2α mutant (rCK2α-△C, 1—335) and CK2β (rCK2β). The overall topology of rCK2α-△C and rCK2β are very similar to the human enzyme, although large structural differences could be observed in the N-terminal domain of rCK2α-△C. Our reported structure of rCK2α-△C is in the close conformation state while the counterpart hCK2α is in the open conformation state, indi- cating the conformation of CK2α molecule has high plasticity. The structure of rCK2β represents the conformation of free CK2β. Upon CK2α binding, the C-terminal region undergoes a drastic conformational change. The major region of interaction within the interface of CK2α/CK2β may serve as a bridge to transmit the conformational change and thus regulate the activity of CK2α.展开更多
文摘Proteins like Raf kinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions, have been demon- strated to play an increasingly important role in a number of cell types and organisms. These proteins have been implicated in development as well as the progression of cancer. RKIP is a particularly interesting regulator, as it is a highly conserved, ubiquitously expressed protein that has been shown to play a role in growth and differentiation in a number of organisms and can regulate multiple signaling pathways. RKIP is also the first MAP kinase signaling modulator to be identified as playing a role in cancer metastasis, and identification of the mechanism by which it regulates Raf-1 activation provides new targets for therapeutic intervention.
基金Supported by Tianjin Basic Research Program (Grant No. 07JCYBJC15600)National Natural Science Foundation of China (Grant No. 30770428)+2 种基金National Key Basic Research and Development Program of China (Grant Nos. 2007CB914301, 2006CB910200)National High-Technology Research and Development Program of China (Grant No. 2006AA02A319)National Institute of Health (Grant No. MH07752)
文摘Protein kinase CK2 consists of two catalytic subunits (CK2α) and two regulatory subunits (CK2β). Here, we report the crystal structures of rat CK2α mutant (rCK2α-△C, 1—335) and CK2β (rCK2β). The overall topology of rCK2α-△C and rCK2β are very similar to the human enzyme, although large structural differences could be observed in the N-terminal domain of rCK2α-△C. Our reported structure of rCK2α-△C is in the close conformation state while the counterpart hCK2α is in the open conformation state, indi- cating the conformation of CK2α molecule has high plasticity. The structure of rCK2β represents the conformation of free CK2β. Upon CK2α binding, the C-terminal region undergoes a drastic conformational change. The major region of interaction within the interface of CK2α/CK2β may serve as a bridge to transmit the conformational change and thus regulate the activity of CK2α.
