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控制粘着斑形成和细胞迁移的整合素特异性信号通路。

Integrin-specific signaling pathways controlling focal adhesion formation and cell migration.

作者信息

Mostafavi-Pour Zohreh, Askari Janet A, Parkinson Scott J, Parker Peter J, Ng Tony T C, Humphries Martin J

机构信息

School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK.

出版信息

J Cell Biol. 2003 Apr 14;161(1):155-67. doi: 10.1083/jcb.200210176.

DOI:10.1083/jcb.200210176
PMID:12695503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2172880/
Abstract

The fibronectin (FN)-binding integrins alpha4beta1 and alpha5beta1 confer different cell adhesive properties, particularly with respect to focal adhesion formation and migration. After analyses of alpha4+/alpha5+ A375-SM melanoma cell adhesion to fragments of FN that interact selectively with alpha4beta1 and alpha5beta1, we now report two differences in the signals transduced by each receptor that underpin their specific adhesive properties. First, alpha5beta1 and alpha4beta1 have a differential requirement for cell surface proteoglycan engagement for focal adhesion formation and migration; alpha5beta1 requires a proteoglycan coreceptor (syndecan-4), and alpha4beta1 does not. Second, adhesion via alpha5beta1 caused an eightfold increase in protein kinase Calpha (PKCalpha) activation, but only basal PKCalpha activity was observed after adhesion via alpha4beta1. Pharmacological inhibition of PKCalpha and transient expression of dominant-negative PKCalpha, but not dominant-negative PKCdelta or PKCzeta constructs, suppressed focal adhesion formation and cell migration mediated by alpha5beta1, but had no effect on alpha4beta1. These findings demonstrate that different integrins can signal to induce focal adhesion formation and migration by different mechanisms, and they identify PKCalpha signaling as central to the functional differences between alpha4beta1 and alpha5beta1.

摘要

纤连蛋白（FN）结合整合素α4β1和α5β1赋予细胞不同的黏附特性，尤其是在黏着斑形成和迁移方面。在分析了α4+/α5+ A375-SM黑色素瘤细胞与FN片段（这些片段能选择性地与α4β1和α5β1相互作用）的黏附情况后，我们现在报告了每种受体转导的信号存在的两个差异，这些差异是它们特定黏附特性的基础。首先，α5β1和α4β1在黏着斑形成和迁移中对细胞表面蛋白聚糖参与的需求存在差异；α5β1需要蛋白聚糖共受体（syndecan-4），而α4β1则不需要。其次，通过α5β1黏附导致蛋白激酶Cα（PKCα）激活增加了八倍，但通过α4β1黏附后仅观察到基础PKCα活性。PKCα的药理学抑制以及显性负性PKCα的瞬时表达，而非显性负性PKCδ或PKCζ构建体，抑制了由α5β1介导的黏着斑形成和细胞迁移，但对α4β1没有影响。这些发现表明，不同的整合素可以通过不同机制发出信号来诱导黏着斑形成和迁移，并且它们确定PKCα信号传导是α4β1和α5β1功能差异的核心。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/d4a2c30a8e7e/200210176f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/983b15199b34/200210176f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/873287875eba/200210176f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/65bf5e0687e3/200210176f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/de6c1a86e44c/200210176f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/c2bb99c851a6/200210176f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/abe803a50891/200210176f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/e1533bc1d3a8/200210176f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/16ae0f9782f5/200210176f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/d4a2c30a8e7e/200210176f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/983b15199b34/200210176f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/873287875eba/200210176f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/65bf5e0687e3/200210176f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/de6c1a86e44c/200210176f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/c2bb99c851a6/200210176f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/abe803a50891/200210176f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/e1533bc1d3a8/200210176f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/16ae0f9782f5/200210176f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bcc/2172880/d4a2c30a8e7e/200210176f9.jpg

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