Deans J P, Kalt L, Ledbetter J A, Schieven G L, Bolen J B, Johnson P
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
J Biol Chem. 1995 Sep 22;270(38):22632-8. doi: 10.1074/jbc.270.38.22632.
CD20, a non-glycosylated cell-surface protein expressed exclusively on B lymphocytes, is one of a family of 4-pass transmembrane molecules that also includes the beta chain of the high affinity receptor for IgE. The precise function of CD20 is unknown, although in vitro effects of CD20-specific antibodies on resting B cells indicate that it is able to transduce an extracellular signal affecting the G0/G1 cell cycle transition. Previous studies have demonstrated that CD20-initiated intracellular signals involve tyrosine kinase activation and that CD20 is tightly associated with both serine and tyrosine kinases. Here, analysis of CD20-associated molecules has revealed that CD20 is associated with the Src family tyrosine kinases p56/53lyn, p56lck, and p59fyn and with 75/80-kDa proteins phosphorylated in vivo on tyrosine residues. Mutagenesis of CD20 was performed to define regions of CD20 involved in intermolecular interactions. Mutants were analyzed in the human T lymphoblastoid cell line Molt-4, in which ectopically expressed wild-type CD20 associated with p59fyn, p56lck, and 75/80-kDa phosphoproteins. Deletion of major portions of the cytoplasmic regions of CD20 did not abolish its association with either p75/80 or tyrosine kinases. The interaction between CD20 and the Src-related kinases is therefore likely to be independent of CD20 cytoplasmic domains and may occur indirectly. The interaction may be mediated by the p75/80 phosphoproteins, which were found to be tightly associated with the Src family kinases isolated from the CD20 complex.
CD20是一种仅在B淋巴细胞上表达的非糖基化细胞表面蛋白，是四跨膜分子家族的一员，该家族还包括IgE高亲和力受体的β链。尽管CD20特异性抗体对静息B细胞的体外作用表明它能够转导影响G0/G1细胞周期转换的细胞外信号，但CD20的确切功能尚不清楚。先前的研究表明，CD20启动的细胞内信号涉及酪氨酸激酶激活，并且CD20与丝氨酸和酪氨酸激酶紧密相关。在这里，对CD20相关分子的分析表明，CD20与Src家族酪氨酸激酶p56/53lyn、p56lck和p59fyn以及体内酪氨酸残基磷酸化的75/80-kDa蛋白相关。对CD20进行诱变以确定其参与分子间相互作用的区域。在人T淋巴母细胞系Molt-4中分析突变体，在该细胞系中异位表达的野生型CD20与p59fyn、p56lck和75/80-kDa磷蛋白相关。删除CD20细胞质区域的主要部分并没有消除其与p75/80或酪氨酸激酶的关联。因此，CD20与Src相关激酶之间的相互作用可能独立于CD20细胞质结构域，并且可能间接发生。这种相互作用可能由p75/80磷蛋白介导，发现它们与从CD20复合物中分离的Src家族激酶紧密相关。
