CD44 is required for two consecutive steps in HGF/c-Met signaling
CD44 is required for two consecutive steps in HGF/c-Met signaling
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DOI：
10.1101/gad.242602
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发表时间：
2002-12-01
影响因子：
10.5
通讯作者：
Ponta, H
中科院分区：
文献类型：
--
作者：
Orian-Rousseau, V;Chen, LF;Ponta, H
The tyrosine kinase receptor c-Met and its ligand HGF/SF, ezrin, and splice variants of CD44 have independently been identified as tumor metastasis-associated proteins. We now show that these proteins cooperate. A CD44 isoform containing variant exon v6 sequences is strictly required for c-Met activation by HGF/SF in rat and human carcinoma cells, in established cell lines as well as in primary keratinocytes. CD44v6-deficient tumor cells were unable to activate c-Met unless they were transfected with a CD44v6-bearing isoform. Antibodies to two v6-encoded epitopes inhibited autophosphorylation of c-Met by interfering with the formation of a complex formed by c-Met, CD44v6, and HGF/SF. In addition, signal transduction from activated c-Met to MEK and Erk required the presence of the cytoplasmic tail of CD44 including a binding motif for ERM proteins. This suggests a role for ERM proteins and possibly their link to the cortical actin cytoskeleton in signal transfer.
