Inhibition of platelet-derived growth factor-BB-induced receptor activation and fibroblast migration by hyaluronan activation of CD44
Inhibition of platelet-derived growth factor-BB-induced receptor activation and fibroblast migration by hyaluronan activation of CD44
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DOI：
10.1074/jbc.m605607200
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发表时间：
2006-09-08
影响因子：
4.8
通讯作者：
Heldin, Paraskevi
中科院分区：
文献类型：
--
作者：
Li, Lingli;Heldin, Carl-Henrik;Heldin, Paraskevi
发现细胞外基质分子透明质酸抑制血小板衍生生长因子（PDGF）β受体活化和PDGF-BB诱导的原代人真皮成纤维细胞迁移。透明质酸的抑制作用被特异性抑制透明质酸与其受体CD 44结合的单克隆抗体中和。此外，免疫共沉淀实验表明，PDGF β-受体和CD 44可以形成复合物。有趣的是，在酪氨酸磷酸酶抑制剂过钒酸盐存在下，未观察到透明质酸对PDGF β受体活化的抑制作用。我们的观察结果表明，透明质酸通过募集CD 44相关的酪氨酸磷酸酶来抑制PDGF β受体的活化。
The extracellular matrix molecule hyaluronan was found to suppress platelet-derived growth factor (PDGF) beta-receptor activation and PDGF-BB-induced migration of primary human dermal fibroblasts. The suppressive effect of hyaluronan was neutralized by a monoclonal antibody that specifically inhibits hyaluronan binding to its receptor CD44. Moreover, co-immunoprecipitation experiments showed that the PDGF beta-receptor and CD44 can form a complex. Interestingly, the inhibitory effect of hyaluronan on PDGF beta-receptor activation was not seen in the presence of the tyrosine phosphatase inhibitor pervanadate. Our observations suggest that hyaluronan suppresses PDGF beta-receptor activation by recruiting a CD44-associated tyrosine phosphatase to the receptor.