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首页> 外文期刊>Molecular and Cellular Biology >Protein Kinase B/Akt Acts via Glycogen Synthase Kinase 3 To Regulate Recycling of αvβ3 and α5β1 Integrins
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Protein Kinase B/Akt Acts via Glycogen Synthase Kinase 3 To Regulate Recycling of αvβ3 and α5β1 Integrins

机译：蛋白激酶B / Akt通过糖原合酶激酶3调节αvβ3和α5β1整联蛋白的循环。

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摘要

Protein kinase B (PKB)/Akt is known to promote cell migration, and this may contribute to the enhanced invasiveness of malignant cells. To elucidate potential mechanisms by which PKB/Akt promotes the migration phenotype, we have investigated its role in the endosomal transport and recycling of integrins. Whereas the internalization of αvβ3 and α5β1 integrins and their transport to the recycling compartment were independent of PKB/Akt, the return of these integrins (but not internalized transferrin) to the plasma membrane was regulated by phosphatidylinositol 3-kinases and PKB/Akt. The blockade of integrin recycling and cell spreading on integrin ligands effected by inhibition of PKB/Akt was reversed by inhibition of glycogen synthase kinase 3 (GSK-3). Moreover, expression of nonphosphorylatable active GSK-3β mutant GSK-3β-A9 suppressed recycling of α5β1 and αvβ3 and reduced cell spreading on ligands for these integrins, indicating that PKB/Akt promotes integrin recycling by phosphorylating and inactivating GSK-3. We propose that the ability of PKB/Akt to act via GSK-3 to promote the recycling of matrix receptors represents a key mechanism whereby integrin function and cell migration can be regulated by growth factors.
机译：已知蛋白激酶B（PKB）/ Akt会促进细胞迁移，这可能有助于增强恶性细胞的侵袭性。为了阐明PKB / Akt促进迁移表型的潜在机制，我们研究了其在内体转运和整联蛋白回收中的作用。尽管αvβ3和α5β1整合素的内在化及其向回收室的运输与PKB / Akt无关，但这些整合素（但不是内在化的转铁蛋白）向质膜的返回却受磷脂酰肌醇3激酶和PKB / Akt的调节。通过抑制糖原合酶激酶3（GSK-3）可以逆转对整联蛋白再循环的阻滞和对整联蛋白配体的细胞扩散的阻断。此外，不可磷酸化的活性GSK-3β突变体GSK-3β-A9的表达抑制了α5β1和αvβ3的再循环，并减少了这些整联蛋白在配体上的细胞扩散，表明PKB / Akt通过磷酸化和灭活GSK-3促进了整联蛋白的再循环。我们提出，PKB / Akt通过GSK-3起作用以促进基质受体循环的能力代表了一个关键机制，其中整联蛋白功能和细胞迁移可以由生长因子调节。

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