Keratin 8/18 modulation of protein kinase C-mediated integrin-dependent adhesion and migration of liver epithelial cells.
Keratin 8/18 modulation of protein kinase C-mediated integrin-dependent adhesion and migration of liver epithelial cells.
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DOI：
10.1091/mbc.e09-05-0373
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发表时间：
2010-05-15
影响因子：
3.3
通讯作者：
Marceau N
中科院分区：
文献类型：
--
作者：
Bordeleau F;Galarneau L;Gilbert S;Loranger A;Marceau N
肝细胞和肝癌细胞IF仅由角蛋白8/18（K8/K18）组成。细胞粘附和迁移涉及整合素与粘着斑激酶（FAK）和蛋白激酶C（PKC）的相互作用。在这里，我们报告了一个新的调节功能的K8/K18 IFs在PKC介导的整合素/FAK依赖的粘附和迁移的简单上皮细胞。角蛋白是上皮细胞的中间丝（IF）蛋白，以谱系/分化方式成对表达。肝细胞和肝癌细胞IF仅由角蛋白8/18（K8/K18）组成，角蛋白8/18是所有简单上皮的标志。细胞附着/铺展（粘附）和迁移涉及在整合素与细胞外基质、肌动蛋白衔接子（如talin和黏着斑蛋白）和信号分子（如粘着斑激酶（FAK）和蛋白激酶C（PKC）家族的成员）相互作用的位点处形成粘着斑。在这里，我们确定了新的PKCδ介导的K8/K18调节肝癌细胞的粘附和迁移。我们还证明了PKCδ和FAK激活之间通过整合素/FAK正反馈环的K8/K18依赖性关系，与FAK在局灶性粘连处停留时间减少相关。值得注意的是，K8/K18损失导致活化的C-激酶-1、β1-整联蛋白、网蛋白、PKC和c-Src复合物形成的受体的时程调节。尽管K8/K18对肝细胞粘附的调节也通过PKC介导发生，但这些分化的上皮细胞表现出最小的迁移能力，与蛋白伴侣含量和分布的显著差异有关。总之，这些结果揭示了K8/K18 IFs在PKC介导的整合素/FAK依赖性粘附和简单上皮细胞迁移中的关键调节功能。
Hepatocyte and hepatoma cell IFs are made solely of keratins 8/18 (K8/K18). Cell adhesion and migration involve integrin interactions with focal adhesion kinase (FAK) and protein kinase C (PKC). Here we report a new regulatory function for K8/K18 IFs in the PKC-mediated integrin/FAK-dependent adhesion and migration of simple epithelial cells. Keratins are intermediate filament (IF) proteins of epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatocyte and hepatoma cell IFs are made solely of keratins 8/18 (K8/K18), the hallmark of all simple epithelia. Cell attachment/spreading (adhesion) and migration involve the formation of focal adhesions at sites of integrin interactions with extracellular matrix, actin adaptors such as talin and vinculin, and signaling molecules such as focal adhesion kinase (FAK) and member(s) of the protein kinase C (PKC) family. Here, we identify the novel PKCδ as mediator of the K8/K18 modulation of hepatoma cell adhesion and migration. We also demonstrate a K8/K18-dependent relationship between PKCδ and FAK activation through an integrin/FAK-positive feedback loop, in correlation with a reduced FAK time residency at focal adhesions. Notably, a K8/K18 loss results to a time course modulation of the receptor of activated C-kinase-1, β1-integrin, plectin, PKC, and c-Src complex formation. Although the K8/K18 modulation of hepatocyte adhesion also occurs through a PKC mediation, these differentiated epithelial cells exhibit minimal migrating ability, in link with marked differences in protein partner content and distribution. Together, these results uncover a key regulatory function for K8/K18 IFs in the PKC-mediated integrin/FAK-dependent adhesion and migration of simple epithelial cells.
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影响因子：
13.5
作者：
Gkretsi, Vasiliki;Mars, Wendy M.;Michalopoulos, George K.
通讯作者：
Michalopoulos, George K.
影响因子：
5.6
作者：
Gagne, David;Groulx, Jean-Francois;Benoit, Yannick D.;Basora, Nuria;Herring, Elizabeth;Vachon, Pierre H.;Beaulieu, Jean-Francois
通讯作者：
Beaulieu, Jean-Francois
DOI：
10.1083/jcb.200709019
发表时间：
2008-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goetz JG;Joshi B;Lajoie P;Strugnell SS;Scudamore T;Kojic LD;Nabi IR
通讯作者：
Nabi IR
DOI：
10.1083/jcb.200602146
发表时间：
2006-07-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ku NO;Omary MB
通讯作者：
Omary MB
影响因子：
8
作者：
Chang, BY;Harte, RA;Cartwright, CA
通讯作者：
Cartwright, CA