神经肽刺激小细胞肺癌细胞系中的酪氨酸磷酸化和酪氨酸激酶活性。

Neuropeptides stimulate tyrosine phosphorylation and tyrosine kinase activity in small cell lung cancer cell lines.

作者信息

Tallett A, Chilvers E R, MacKinnon A C, Haslett C, Sethi T

机构信息

Respiratory Medicine Unit (RIE), Rayne Laboratory, University of Edinburgh Medical School, UK.

出版信息

Peptides. 1996;17(4):665-73. doi: 10.1016/0196-9781(96)00055-1.

DOI:10.1016/0196-9781(96)00055-1

PMID:8804078

Abstract

Stimulation of small cell lung cancer (SCLC) cells with neuropeptides bombesin, bradykinin, gastrin, and neurotensin resulted in increased tyrosine kinase activity and tyrosine phosphorylation of a number of polypeptides including a p120 kDa polypeptide identified by immunoblotting as focal adhesion kinase (p125FAK). The neuropeptides stimulated a rapid, concentration-dependent phosphorylation of p125FAK (EC50 of 1 nM, 5 nM, and 2 nM for bombesin, bradykinin, and gastrin, respectively), which was receptor mediated and inhibited by both specific and broad-spectrum neuropeptide receptor antagonists. Specific inhibition of protein tyrosine kinase activity by tyrphostin-25 inhibited both basal and neuropeptide-stimulated SCLC cell growth. These results identify a novel neuropeptide-stimulated growth signaling event in SCLC cells.

摘要

用神经肽蛙皮素、缓激肽、胃泌素和神经降压素刺激小细胞肺癌（SCLC）细胞，导致酪氨酸激酶活性增加，以及包括通过免疫印迹鉴定为粘着斑激酶（p125FAK）的一种120 kDa多肽在内的多种多肽发生酪氨酸磷酸化。这些神经肽刺激p125FAK发生快速、浓度依赖性磷酸化（蛙皮素、缓激肽和胃泌素的EC50分别为1 nM、5 nM和2 nM），这是由受体介导的，并且受到特异性和广谱神经肽受体拮抗剂的抑制。酪氨酸磷酸化酶-25对蛋白酪氨酸激酶活性的特异性抑制同时抑制了基础状态和神经肽刺激的SCLC细胞生长。这些结果确定了SCLC细胞中一种新的神经肽刺激的生长信号事件。