Inhibitory role of alpha 6 beta 4-associated erbB-2 and phosphoinositide 3-kinase in keratinocyte haptotactic migration dependent on alpha 3 beta 1 integrin.
Inhibitory role of alpha 6 beta 4-associated erbB-2 and phosphoinositide 3-kinase in keratinocyte haptotactic migration dependent on alpha 3 beta 1 integrin.
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DOI：
10.1083/jcb.153.3.465
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发表时间：
2001-04-30
期刊：
影响因子：
--
通讯作者：
Quaranta V
中科院分区：
文献类型：
--
作者：
Hintermann E;Bilban M;Sharabi A;Quaranta V
角质形成细胞和其他上皮细胞表达基底膜细胞外基质成分层粘连蛋白-5(Ln-5)的两种受体，整合素α3β1和α6β4。而α3β1介导黏附、扩散和迁移(Kreidberg，J.A.2000)。货币。奥平。细胞生物。12：548-553)，α6β4通过半桥粒(Borradori，L.和A.Sonnenberg)参与BM锚定。1999年。J.投资。皮肤素。112：411-418)。我们以HaCaT角质形成细胞为模型，研究了α-3-β-1和α-6-β-4在细胞运动中可能的调控相互作用。我们发现，α6β4抗体抑制α3β1介导的Ln-5迁移，但仅当迁移是突触性的(即自发的或由α3β1激活刺激的)时，而不是趋化性的(即由表皮生长因子受体触发的)。α6β4对迁移的抑制依赖于磷脂酰肌醇3-K(PI3-K)，因为PI3-K被PI3-K阻滞剂和显性负性PI3-K所消除，而结构性活性PI3-K阻止触觉趋化。在与抗α6β4抗体共同孵育的HaCaT细胞中，α6β4相关的Erb B-2通过Erb B-2自身磷酸化和Erb B-2/P85 PI3-K共沉淀介导了PI3-K的激活。此外，显性阴性的erbB-2可取消抗α-6β-4抗体对亲和力的抑制。这些结果支持一个模型，即：(A)Ln-5上的趋化细胞迁移受α3β1和α6β4整合素的协同作用调节，(B)α6β4相关的Erb B-2和PI3-K负向影响Ln-5上的趋化作用，(C)Ln-5上的趋化不受α6β4抗体的影响，可能需要PI3-K活性。这一模型可能对接触骨髓的上皮细胞的运动具有普遍的相关性。
Keratinocytes and other epithelial cells express two receptors for the basement membrane (BM) extracellular matrix component laminin-5 (Ln-5), integrins α3β1 and α6β4. While α3β1 mediates adhesion, spreading, and migration (Kreidberg, J.A. 2000. Curr. Opin. Cell Biol. 12:548–553), α6β4 is involved in BM anchorage via hemidesmosomes (Borradori, L., and A. Sonnenberg. 1999. J. Invest. Dermatol. 112:411–418). We investigated a possible regulatory interplay between α3β1 and α6β4 in cell motility using HaCaT keratinocytes as a model. We found that α6β4 antibodies inhibit α3β1-mediated migration on Ln-5, but only when migration is haptotactic (i.e., spontaneous or stimulated by α3β1 activation), and not when chemotactic (i.e., triggered by epidermal growth factor receptor). Inhibition of migration by α6β4 depends upon phosphoinositide 3-kinase (PI3-K) since it is abolished by PI3-K blockers and by dominant-negative PI3-K, and constitutively active PI3-K prevents haptotaxis. In HaCaT cells incubated with anti–α6β4 antibodies, activation of PI3-K is mediated by α6β4-associated erbB-2, as indicated by erbB-2 autophosphorylation and erbB-2/p85 PI3-K coprecipitation. Furthermore, dominant-negative erbB-2 abolishes inhibition of haptotaxis by anti–α6β4 antibodies. These results support a model whereby (a) haptotactic cell migration on Ln-5 is regulated by concerted action of α3β1 and α6β4 integrins, (b) α6β4-associated erbB-2 and PI3-K negatively affect haptotaxis, and (c) chemotaxis on Ln-5 is not affected by α6β4 antibodies and may require PI3-K activity. This model could be of general relevance to motility of epithelial cells in contact with BM.
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影响因子：
7.8
作者：
Blystone, S D;Graham, I L;Lindberg, F P;Brown, E J
通讯作者：
Brown, E J
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影响因子：
7.8
作者：
Carter, W G;Kaur, P;Gil, S G;Gahr, P J;Wayner, E A
通讯作者：
Wayner, E A
影响因子：
4.8
作者：
Gambaletta, D;Marchetti, A;Falcioni, R
通讯作者：
Falcioni, R
影响因子：
3.5
作者：
Alroy, I;Yarden, Y
通讯作者：
Yarden, Y
DOI：
10.1083/jcb.141.1.255
发表时间：
1998-04-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goldfinger LE;Stack MS;Jones JC
通讯作者：
Jones JC