Induction of EGFR-dependent and EGFR-independent signaling pathways by ultraviolet A irradiation.
Induction of EGFR-dependent and EGFR-independent signaling pathways by ultraviolet A irradiation.
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通过紫外线 A 照射诱导 EGFR 依赖性和 EGFR 非依赖性信号通路。
DOI：
10.1089/104454901753438589
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发表时间：
2001
影响因子：
3.1
通讯作者：
Dong,Z
中科院分区：
文献类型：
--
作者：
Zhang,Y;Dong,Z;Bode,AM;Ma,WY;Chen,N;Dong,Z
大多数参与紫外线（UV）诱发皮肤癌的信号通路被认为起源于质膜受体。然而，uva诱导的下游核糖体蛋白S6激酶p70s6and p90RSK的信号转导尚不清楚。在本报告中，我们发现UVA刺激表皮生长因子受体（EGFR）可能通过磷脂酰异糖醇(PI)-3激酶和细胞外受体活化激酶（ERKs）激活p70S6K/ p90rsk。有证据表明，UVA诱导的p70S6K/ p90rsk的磷酸化和活化在egfr -/-细胞中被阻止，并被egfr特异性酪氨酸激酶抑制剂AG1478和PD153035显著抑制。此外，EGFR酪氨酸激酶抑制剂和EGFR缺乏显著抑制PI-3激酶和ERKs的激活，以调节p90RSK/ p70s6kk的激活，但对c-Jun nh2末端激酶（JNKs）和p38激酶的激活没有影响。因此，我们的研究结果表明，uva诱导的EGFR信号通路可能是激活p90RSK/p70S6K、PI-3激酶和ERKs而不是JNKs或p38激酶所必需的。
Most of the signal pathways involved in ultraviolet (UV)-induced skin carcinogenesis are thought to originate at plasma membrane receptors. However, UVA-induced signal transduction to downstream ribosomal protein S6 kinases, p70S6Kand p90RSK, is not well understood. In this report, we show that UVA stimulation of the epidermal growth factor receptor (EGFR) may lead to activation of p70S6K/p90RSKthrough phosphatidyl isositol (PI)-3 kinase and extracellular receptor-activated kinases (ERKs). Evidence is provided that phosphorylation and activation of p70S6K/p90RSKinduced by UVA were prevented inEgfr-/-cells and were also markedly inhibited by the EGFR-specific tyrosine kinase inhibitors AG1478 and PD153035. Furthermore, EGFR tyrosine kinase inhibitors and EGFR deficiency significantly suppressed activation of PI-3 kinase and ERKs in regulating activation of p90RSK/p70S6Kbut had no effect on activation of c-Jun NH2-terminal kinases (JNKs) and p38 kinase in response to UVA. Thus, our results suggest that UVA-induced EGFR signaling may be required for activation of p90RSK/p70S6K, PI-3 kinase, and ERKs but not JNKs or p38 kinase.