Vav binding to heterogeneous nuclear ribonucleoprotein (hnRNP) C - Evidence for Vav-hnRNP interactions in an RNA-dependent manner
Vav binding to heterogeneous nuclear ribonucleoprotein (hnRNP) C - Evidence for Vav-hnRNP interactions in an RNA-dependent manner
复制标题
DOI：
10.1074/jbc.273.10.5923
复制
发表时间：
1998-03-06
影响因子：
4.8
通讯作者：
Fischer, S
中科院分区：
文献类型：
--
作者：
Romero, F;Germani, A;Fischer, S
Vav原癌基因仅在造血细胞中表达，编码一种含有多个结构域的95-kDa蛋白。Vav参与T和B细胞的扩增、抗原介导的增殖反应以及胸腺内T细胞成熟的诱导。Vav在Rac-1表面被大量受体激活后迅速、短暂地酪氨酸磷酸化，催化GDP/GTP交换。Vav和hnRNP C通过Vav的羧基Src同源3结构域和位于hnRNP C核保留序列中的富含脯氨酸的基序介导在体内和体外相互作用。更重要的是，Vav-hnRNP C复合物存在于活的造血细胞中，并且这两种蛋白质都定位于细胞核中，主要在染色质周围纤维上，但也在染色质间颗粒簇上。Vav-hnRNP C相互作用受poly（U）RNA调节，尽管在不存在RNA的情况下仍检测到基础缔合。此外，RNA均聚物差异地改变Vav与hnRNP C和hnRNP K的结合亲和力，我们提出Vav与hnRNP的相互作用可能以RNA依赖的方式建立。
The vav proto-oncogene is exclusively expressed in hematopoietic cells and encodes a 95-kDa protein that contains multiple structural domains, Vav is involved in the expansion of T and B cells, in antigen-mediated proliferative responses, and in the induction of intrathymic T cell maturation. It becomes rapidly and transiently tyrosine-phosphorylated upon triggering of a large number of surface receptors and catalyzes GDP/GTP exchange on Rac-1, We now provide evidence for the specific interaction of Vav with heterogeneous nuclear ribonucleoprotein (hnRNP) C. Vav and hnRNP C interact both in vivo and in vitro mediated through the carboxyl Src homology 3 domain of Vav and the proline-rich motif located in the nuclear retention sequence of hnRNP C. More importantly, Vav-hnRNP C complexes are present in living hematopoietic cells and both proteins localize in the nuclei, mainly on perichromatic fibrils but also on clusters of interchromatin granules. The Vav-hnRNP C interaction is regulated by poly(U) RNA although a basal association is still detected in the absence of RNA. Furthermore, RNA homopolymers differentially alter the binding affinity of Vav to hnRNP C and hnRNP K, We propose that Vav-hnRNP interactions may be established in an RNA-dependent manner.