Liu W, Youn H D, Zhou X Z, Lu K P, Liu J O
Center for Cancer Research, Departments of Biology and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
FEBS Lett. 2001 May 11;496(2-3):105-8. doi: 10.1016/s0014-5793(01)02411-5.
Nuclear factor of activated T cells (NFAT) plays a key role in T cell activation. The activation of NFAT involves calcium- and calcineurin-dependent dephosphorylation and nuclear translocation from the cytoplasm, a process that is opposed by protein kinases. We show here that the peptidyl prolyl cis-trans isomerase Pin1 interacts specifically with the phosphorylated form of NFAT. The NFAT-Pin1 interaction is mediated through the WW domain of Pin1 and the serine-proline-rich domains of NFAT. Furthermore, binding of Pin1 to NFAT inhibits the calcineurin-mediated dephosphorylation of NFAT in vitro, and overexpression of Pin1 in T cells inhibits calcium-dependent activation of NFAT in vivo. These results suggest a possible role for Pin1 in the regulation of NFAT in T cells.
活化T细胞核因子（NFAT）在T细胞活化过程中发挥关键作用。NFAT的活化涉及钙和钙调神经磷酸酶依赖性的去磷酸化以及从细胞质向细胞核的转位，这一过程受到蛋白激酶的抑制。我们在此表明，肽基脯氨酰顺反异构酶Pin1特异性地与NFAT的磷酸化形式相互作用。NFAT与Pin1的相互作用是通过Pin1的WW结构域和NFAT富含丝氨酸 - 脯氨酸的结构域介导的。此外，Pin1与NFAT的结合在体外抑制了钙调神经磷酸酶介导的NFAT去磷酸化，并且在T细胞中过表达Pin1在体内抑制了NFAT的钙依赖性活化。这些结果表明Pin1在T细胞中NFAT的调节中可能发挥作用。
