Regulation of hyaluronan binding by F-actin and colocalization of CD44 and phosphorylated ezrin/radixin/moesin (ERM) proteins in myeloid cells
Regulation of hyaluronan binding by F-actin and colocalization of CD44 and phosphorylated ezrin/radixin/moesin (ERM) proteins in myeloid cells
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DOI：
10.1016/j.yexcr.2004.10.002
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发表时间：
2005-02-15
影响因子：
3.7
通讯作者：
Johnson, P
中科院分区：
文献类型：
--
作者：
Brown, KL;Birkenhead, D;Johnson, P
促炎性细胞因子如TNF-α上调细胞粘附分子CD 44的表达，并诱导外周血单核细胞（PBM）中的透明质酸（HA）结合。在PBM中，TNF-α诱导细胞骨架重排，增加ERM蛋白的苏氨酸磷酸化，并诱导磷酸化ERM蛋白（P-ERM）与CD 44的再分布和共定位。在髓系祖细胞系KG 1a中，透明质酸结合发生在伪足中，其中CD 44、P-ERM。和F-肌动蛋白高度定位。Hybryonan结合与CD 44和P-ERM的高表达相关，在单个伪足中表达。破坏聚合肌动蛋白减少透明质酸结合在PBM和KG 1a细胞和取消CD 44聚集和伪足在KG 1a细胞。CD 44的聚集、与P-ERM的共定位或透明质酸结合不需要伪足。然而，用激酶抑制剂治疗废除了ERM磷酸化并减少了透明质酸结合。此外，缺乏推定的ERM结合位点的CD 44的表达导致透明质酸结合减少。总之，这些数据表明，CD 44介导的透明质酸结合在人骨髓细胞的P-ERM和肌动蛋白细胞骨架的调节。(C)2004年爱思唯尔公司All rights reserved.
Proinflammitatory cytokines such as TNF-alpha up-regulate the expression of the cell adhesion molecule, CD44, and induce hyaluronan (HA) binding in peripheral blood monocytes (PBM). Here we show that in PBM, TNF-a induced cytoskeletal rearrangement, increased threonine phosphorylation of ERM proteins, and induced the redistribution and colocalization of phospho-ERM proteins (P-ERM) with CD44. In the myeloid progenitor cell line, KG1a, hyaluronan binding occurred in the pseudopod where CD44, P-ERM. and F-actin were highly localized. Hyaluronan binding correlated with high expression of both CD44 and P-ERM Clustered in a single pseudopod. Disruption of polymerized actin reduced hyaluronan binding in both PBM and KG1a cells and abolished CD44 clustering and the pseudopod in KG1a cells. The pseudopod was not required for the clustering of CD44, the colocalization with P-ERM, or hyaluronan binding. However, treatment with a kinase inhibitor abolished ERM phosphorylation and reduced hyaluronan binding. Furthermore, expression of CD44 lacking the putative ERM binding site resulted in reduced hyaluronan binding. Taken together, these data suggest that CD44-mediated hyaluronan binding in human myeloid cells is regulated by P-ERM and the actin cytoskeleton. (C) 2004 Elsevier Inc. All rights reserved.