Bardelli Claudio, Sala Marilena, Cavallazzi Umberto, Prat Maria
Dipt. Scienze Mediche, Università del Piemonte Orientale A. Avogadro Via Solaroli 17, 28100 Novara, Italy.
Biochem Biophys Res Commun. 2005 Sep 9;334(4):1172-9. doi: 10.1016/j.bbrc.2005.07.020.
We previously showed that the Kaposi Sarcoma line KS-IMM express a functional Met tyrosine kinase receptor, which, upon HGF stimulation, activates motogenic, proliferative, and invasive responses. In this study, we investigated the signalling pathways activated by HGF, as well as by Met monoclonal antibodies (Mabs), acting as full or partial agonists. The full agonist Mab mimics HGF in all biological and biochemical aspects. It elicits the whole spectrum of responses, while the partial agonist Mab induces only wound healing. These differences correlated with a more prolonged and sustained tyrosine phosphorylation of the receptor and MAPK evoked by HGF and by the full agonist Mab, relative to the partial agonist Mab. Since Gab1, JNK and PI 3-kinase are activated with same intensity and kinetics by HGF and by the two agonist antibodies, it is concluded that level and duration of MAPK activation by Met receptor are crucial for the induction of a full HGF-dependent mitogenic and invasive program in KS cells.
我们之前发现卡波西肉瘤细胞系KS-IMM表达一种功能性的Met酪氨酸激酶受体，该受体在肝细胞生长因子（HGF）刺激下，可激活促运动、增殖和侵袭反应。在本研究中，我们研究了HGF以及作为完全或部分激动剂的Met单克隆抗体（Mab）所激活的信号通路。完全激动剂Mab在所有生物学和生化方面都模拟HGF。它能引发全谱反应，而部分激动剂Mab仅诱导伤口愈合。这些差异与HGF和完全激动剂Mab相对于部分激动剂Mab所引起的受体和丝裂原活化蛋白激酶（MAPK）酪氨酸磷酸化的时间延长和持续有关。由于Gab1、c-Jun氨基末端激酶（JNK）和磷脂酰肌醇-3激酶（PI 3-激酶）被HGF和两种激动剂抗体以相同强度和动力学激活，因此得出结论，Met受体激活MAPK的水平和持续时间对于在KS细胞中诱导完整的HGF依赖性促有丝分裂和侵袭程序至关重要。
