Yelo Estefanía, Bernardo María Victoria, Gimeno Lourdes, Alcaraz-García María José, Majado María Juliana, Parrado Antonio
Servicio de Inmunologia, Hospital Universitario Virgen de la Arrixaca, Ctra. Madrid-Cartagena s/n, El Palmar, 30120 Murcia, Spain.
Mol Immunol. 2008 Jul;45(12):3411-8. doi: 10.1016/j.molimm.2008.04.003. Epub 2008 May 21.
The Dock or CZH proteins are a family of activators for Rho GTPase proteins. The Zizimin subfamily is composed of three members: Dock9, Dock10, and Dock11. We have identified DOCK10 as an interleukin-4 (IL4)-inducible gene in chronic lymphocytic leukemias (CLLs). Subsequently, we have obtained the full-length cDNA sequence, which encodes a 2180 amino acid protein. Dock9 (2069 amino acids) and Dock11 (2073 amino acids) share more identity between them (58%) than with Dock10 (52% and 50%, respectively). Among normal human tissues, DOCK10 and DOCK11 mRNAs were mainly expressed in peripheral blood (PB) leukocytes. Dock10 protein was expressed at similar levels in normal PB-B and PB-T cells. Dock10 protein levels were heterogeneous in CLLs. IL4 consistently increased Dock10 mRNA and protein levels in CLL and normal PB-B cells. In contrast, IL4 did not affect the levels of Dock10 expression in normal PB-T cells. IL4 neither increased DOCK9 or DOCK11 mRNA levels in CLL cells. Dock10 protein distributed in the cytoplasm and nucleus of CLL cells, and IL4 increased its expression in both cellular compartments. The rapid and distinctive induction of Dock10 expression by IL4 in CLL and normal PB-B cells suggests a role for Dock10 in IL4-induced B-cell activation. Dock10 could represent a point of convergence for IL4 signalling and small Rho GTPase function in B cells.
Dock或CZH蛋白是Rho GTPase蛋白的激活剂家族。Zizimin亚家族由三个成员组成：Dock9、Dock10和Dock11。我们已将DOCK10鉴定为慢性淋巴细胞白血病（CLL）中白细胞介素-4（IL4）诱导型基因。随后，我们获得了全长cDNA序列，其编码一个含有2180个氨基酸的蛋白质。Dock9（2069个氨基酸）和Dock11（2073个氨基酸）之间的同源性（58%）高于它们与Dock10的同源性（分别为52%和50%）。在正常人体组织中，DOCK10和DOCK11 mRNA主要在外周血（PB）白细胞中表达。Dock10蛋白在正常PB-B细胞和PB-T细胞中的表达水平相似。Dock10蛋白水平在CLL中存在异质性。IL4持续增加CLL和正常PB-B细胞中Dock10 mRNA和蛋白水平。相比之下，IL4不影响正常PB-T细胞中Dock10的表达水平。IL4也不增加CLL细胞中DOCK9或DOCK11 mRNA水平。Dock10蛋白分布于CLL细胞的细胞质和细胞核中，IL4增加其在两个细胞区室中的表达。IL4在CLL和正常PB-B细胞中对Dock10表达的快速且独特的诱导表明Dock10在IL4诱导的B细胞激活中发挥作用。Dock10可能代表了B细胞中IL4信号传导和小Rho GTPase功能的交汇点。
