Schwartz M A, Lechene C, Ingber D E
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7849-53. doi: 10.1073/pnas.88.17.7849.
Growth of anchorage-dependent cells requires both soluble mitogens and insoluble extracellular matrix molecules such as fibronectin. Soluble growth factors activate chemical signaling pathways and stimulate proliferation by binding to transmembrane receptors. Insoluble fibronectin also binds to cell-surface receptors; however, it is thought to act primarily via effects on the cytoskeleton and cell shape. We recently demonstrated that cell spreading on surface-adsorbed fibronectin activates the Na/H antiporter and that inhibition of this chemical-signaling pathway suppresses growth. We now show that insoluble fibronectin activates the Na/H antiporter by clustering and immobilizing integrin alpha 5 beta 1, independent of effects on cell shape. These results show that an extracellular matrix receptor can behave similarly to a growth factor receptor to activate a signaling pathway implicated in growth control.
锚定依赖性细胞的生长既需要可溶性促有丝分裂原，也需要不溶性细胞外基质分子，如纤连蛋白。可溶性生长因子通过与跨膜受体结合来激活化学信号通路并刺激增殖。不溶性纤连蛋白也能与细胞表面受体结合；然而，人们认为它主要通过对细胞骨架和细胞形状的影响发挥作用。我们最近证明，细胞在表面吸附的纤连蛋白上铺展会激活钠/氢反向转运体，并且抑制这条化学信号通路会抑制生长。我们现在表明，不溶性纤连蛋白通过聚集并固定整联蛋白α5β1来激活钠/氢反向转运体，这与对细胞形状的影响无关。这些结果表明，一种细胞外基质受体的行为可以与生长因子受体类似，以激活一条与生长控制有关的信号通路。
