Ramesh N, Antón I M, Hartwig J H, Geha R S
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14671-6. doi: 10.1073/pnas.94.26.14671.
Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency caused by mutations that affect the WAS protein (WASP) and characterized by cytoskeletal abnormalities in hematopoietic cells. By using the yeast two-hybrid system we have identified a proline-rich WASP-interacting protein (WIP), which coimmunoprecipitated with WASP from lymphocytes. WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs. Expression of WIP in human B cells, but not of a WIP truncation mutant that lacks the actin binding motif, increased polymerized actin content and induced the appearance of actin-containing cerebriform projections on the cell surface. These results suggest that WIP plays a role in cortical actin assembly that may be important for lymphocyte function.
威斯科特-奥尔德里奇综合征(WAS)是一种X连锁免疫缺陷病,由影响威斯科特-奥尔德里奇综合征蛋白(WASP)的突变引起,其特征为造血细胞中的细胞骨架异常。通过使用酵母双杂交系统,我们鉴定出一种富含脯氨酸的WASP相互作用蛋白(WIP),它可与淋巴细胞中的WASP进行共免疫沉淀。WIP在一个不同于Cdc42结合位点的部位与WASP结合,并且具有肌动蛋白以及肌动蛋白结合蛋白结合基序。WIP在人B细胞中的表达增加了聚合肌动蛋白的含量,并诱导细胞表面出现含肌动蛋白的脑回样突起,但缺乏肌动蛋白结合基序的WIP截短突变体则没有这种作用。这些结果表明,WIP在皮层肌动蛋白组装中发挥作用,这可能对淋巴细胞功能很重要。