Kissil Joseph L, Wilker Erik W, Johnson Kristen C, Eckman Matthew S, Yaffe Michael B, Jacks Tyler
Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mol Cell. 2003 Oct;12(4):841-9. doi: 10.1016/s1097-2765(03)00382-4.
The Nf2 tumor suppressor gene codes for merlin, a protein whose function has been elusive. We describe a novel interaction between merlin and p21-activated kinase 1 (Pak1), which is dynamic and facilitated upon increased cellular confluence. Merlin inhibits the activation of Pak1, as the loss of merlin expression results in the inappropriate activation of Pak1 under conditions associated with low basal activity. Conversely, the overexpression of merlin in cells that display a high basal activity of Pak1 resulted in the inhibition of Pak1 activation. This inhibitory function of merlin is mediated through its binding to the Pak1 PBD and by inhibiting Pak1 recruitment to focal adhesions. This link provides a possible mechanism for the effect of loss of merlin expression in tumorigenesis.
神经纤维瘤病2型（Nf2）肿瘤抑制基因编码一种名为默林（merlin）的蛋白质，其功能一直难以捉摸。我们描述了默林与p21激活激酶1（Pak1）之间一种新的相互作用，这种相互作用是动态的，并且在细胞汇合增加时会得到促进。默林抑制Pak1的激活，因为在基础活性较低的条件下，默林表达缺失会导致Pak1的不适当激活。相反，在显示出高基础活性的Pak1的细胞中默林的过表达导致Pak1激活受到抑制。默林的这种抑制功能是通过其与Pak1的PBD结合以及抑制Pak1向粘着斑的募集来介导的。这种联系为默林表达缺失在肿瘤发生中的作用提供了一种可能的机制。
