Wnt-5a and G-protein signaling are required for collagen-induced DDR1 receptor activation and normal mammary cell adhesion
Wnt-5a and G-protein signaling are required for collagen-induced DDR1 receptor activation and normal mammary cell adhesion
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DOI：
10.1002/ijc.10752
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发表时间：
2003-01-20
影响因子：
6.4
通讯作者：
Andersson, T
中科院分区：
文献类型：
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作者：
Dejmek, J;Dib, K;Andersson, T
在表达Wnt-5a的HB 2乳腺细胞中，胶原诱导的盘状结构域受体I（DDRI）磷酸化被百日咳毒素有效抑制，但不被霍乱毒素或阻断β 1整合素的抗体抑制。此外，百日咳毒素使细胞与胶原蛋白的粘附减少了约50%，并且针对β（1）整联蛋白的抗体具有类似的效果，实际上是百日咳毒素的添加剂。因此，霍乱毒素对粘附没有这种影响。相比之下，百日咳毒素不影响Wnt-5a-反义HB 2细胞或MCF-7乳腺肿瘤细胞的粘附，这两种细胞都不表达Wnt-5a或表现出DDRI的活化。根据这些结果，在Wnt-Sa缺陷型MCF-7细胞中，直接mastoparan诱导的G蛋白活化能够使胶原诱导的DDRI磷酸化并增强其粘附。非活性类似物mastoparan-17对MCF-7细胞没有这种作用，活性mastoparan也不影响表达Wnt-5a的HB 2细胞的粘附。一个可能的解释DDRI，受体酪氨酸激酶（RTK），如何加强乳腺细胞粘附来自我们的观察，百日咳毒素也抑制招聘的细胞骨架调节磷脂酰肌醇3-激酶（PI 3 K）DDRI以及其磷酸化/激活。与此一致，PI 3 K抑制剂wortmannin显著损害正常Wnt-5a表达HB 2细胞的粘附，但对Wnt-5a反义HB 2细胞的粘附几乎没有影响。因此，G（i/o）-蛋白信号传导途径通过使胶原蛋白诱导的DDRI活化来介导Wnt-5a表达的作用，DDRI与整合素平行调节乳腺细胞的粘附。(C)2002年威利-利斯。Inc.
The collagen-induced phosphorylation of discoidin domain receptor I (DDRI) in Wnt-5a-expressing HB2 mammary cells was effectively inhibited by pertussis toxin, but not by cholera toxin or antibodies blocking beta(1) integrins. Moreover, pertussis toxin reduced adhesion of the cells to collagen by approximately 50%, and antibodies against beta(1) integrins had a similar effect that was in fact additive to that of pertussis toxin. Cholera toxin had accordingly no such effect on adhesion. By comparison, pertussis toxin did not influence adhesion of Wnt-5a-antisense HB2 cells or MCF-7 mammary tumor cells, neither of which express Wnt-5a or exhibit activation of DDRI. In accordance with these results, direct mastoparan-induced activation of G-proteins in Wnt-Sa-deficient MCF-7 cells enabled collagen-induced phosphorylation of DDRI and enhanced their adhesion. The inactive analogue mastoparan-17 had no such effects on MCF-7 cells nor did active mastoparan affect adhesion of Wnt-5a-expressing HB2 cells. A possible explanation for how DDRI, a receptor tyrosine kinase (RTK), potentiates mammary cell adhesion comes from our observations that pertussis toxin also inhibited the recruitment of the cytoskeletal regulator phosphatidylinositol 3-kinase (PI3K) to DDRI as well as its phosphorylation/activation. In accordance with that, the PI3K inhibitor wortmannin significantly impaired adhesion of normal Wnt-5a-expressing HB2 cells but had little effect on adhesion of Wnt-5a-antisense HB2 cells. Thus, a G(i/o)-protein signaling pathway mediates the effect of Wnt-5a expression by enabling collagen-induced activation of DDRI, which, in parallel with 0, integrins, regulates adhesion of mammary cells. (C) 2002 Wiley-Liss. Inc.