Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, PR China; Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, PR China.
Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, PR China.
Biochem Biophys Res Commun. 2014 Mar 28;446(1):25-9. doi: 10.1016/j.bbrc.2014.02.027. Epub 2014 Feb 13.
Tissue kallikrein (TK) is well known to take most of its biological functions through bradykinin receptors. In the present study, we found a novel signaling pathway mediated by TK through epidermal growth factor receptor (EGFR) in human SH-SY5Y cells. We discovered that TK facilitated the activation of EGFR, extracellular signal-regulated kinase (ERK) 1/2 and p38 cascade. Interestingly, not p38 but ERK1/2 phosphorylation was severely compromised in cells depleted of EGFR. Nevertheless, impairment of signaling of ERK1/2 seemed not to be restricted to EGFR phosphorylation. We also observed that TK stimulation could induce SH-SY5Y cell proliferation, which was reduced by EGFR down-regulation or ERK1/2 inhibitor. Overall, our findings provided convincing evidence that TK could mediate cell proliferation via EGFR and ERK1/2 pathway in vitro.
组织激肽释放酶（TK）通过缓激肽受体发挥其大部分生物学功能已广为人知。在本研究中，我们在人 SH-SY5Y 细胞中发现了一条由 TK 通过表皮生长因子受体（EGFR）介导的新信号通路。我们发现 TK 促进了 EGFR、细胞外信号调节激酶（ERK）1/2 和 p38 级联的激活。有趣的是，在 EGFR 耗尽的细胞中，磷酸化 p38 而不是 ERK1/2 严重受损。然而，ERK1/2 信号的损伤似乎并不仅限于 EGFR 磷酸化。我们还观察到 TK 刺激可诱导 SH-SY5Y 细胞增殖，而 EGFR 下调或 ERK1/2 抑制剂可减少这种增殖。总的来说，我们的研究结果提供了令人信服的证据，表明 TK 可以通过体外的 EGFR 和 ERK1/2 途径介导细胞增殖。
