黏着斑激酶（FAK）的过表达通过蛋白激酶C（PKC）和磷脂酰肌醇-3激酶-蛋白激酶B（PI3-激酶-Akt）途径上调细胞周期蛋白D3并增强细胞增殖。

FAK overexpression upregulates cyclin D3 and enhances cell proliferation via the PKC and PI3-kinase-Akt pathways.

作者信息

Yamamoto Daisuke, Sonoda Yoshiko, Hasegawa Maki, Funakoshi-Tago Megumi, Aizu-Yokota Eriko, Kasahara Tadashi

机构信息

Department of Biochemistry, Kyoritsu College of Pharmacy, Shibakoen 1-5-30, Minato-ku, Tokyo 105-8512, Japan.

出版信息

Cell Signal. 2003 Jun;15(6):575-83. doi: 10.1016/s0898-6568(02)00142-0.

DOI:10.1016/s0898-6568(02)00142-0

PMID:12681445

Abstract

We previously demonstrated that FAK-transfected HL-60 (HL-60/FAK) cells exhibit anti-apoptotic capacity. Here, we report that HL-60/FAK cells proliferate much faster than vector-transfected control (HL-60/Vect) cells with a 1.5-fold faster doubling time. This observation prompted us to investigate the mechanism of how HL-60/FAK cells augment cell proliferation. Since a protein kinase C (PKC) inhibitor, chelerythrine, or a PI3-kinase inhibitor, LY294002, suppressed cell proliferation effectively, both PKC and PI-3-kinase pathways are presumed to be involved in the cell proliferation. Among cyclins and CDKs, cyclin D3 expression was particularly prominent in the HL-60/FAK cells. Among PKC family, particularly PKCalpha, beta and eta isoforms were activated and directly associated with FAK in HL-60/FAK cells. We assumed that FAK activates PKC and PI3-kinase-Akt pathway, which resulted in marked induction of cyclin D3 expression and CDK activity.

摘要

我们之前证明，转染了黏着斑激酶（FAK）的HL-60（HL-60/FAK）细胞具有抗凋亡能力。在此，我们报告HL-60/FAK细胞的增殖速度比转染载体的对照（HL-60/Vect）细胞快得多，其倍增时间快1.5倍。这一观察结果促使我们研究HL-60/FAK细胞增强细胞增殖的机制。由于蛋白激酶C（PKC）抑制剂白屈菜红碱或PI3激酶抑制剂LY294002能有效抑制细胞增殖，因此推测PKC和PI-3激酶途径均参与细胞增殖。在细胞周期蛋白和周期蛋白依赖性激酶（CDK）中，细胞周期蛋白D3在HL-60/FAK细胞中的表达尤为突出。在PKC家族中，特别是PKCα、β和η亚型在HL-60/FAK细胞中被激活并与FAK直接相关。我们推测FAK激活PKC和PI3激酶-Akt途径，这导致细胞周期蛋白D3表达和CDK活性显著诱导。