2012年8月17日 訊 /生物谷BIOON/ --我們機(jī)體中的細(xì)胞不斷進(jìn)行著破碎-死亡-再生的過程，相比自相殘殺,，細(xì)胞中的蛋白質(zhì)常常會(huì)破碎分裂成為細(xì)胞的氨基酸組分,，其扮演著細(xì)胞生長和更新的結(jié)構(gòu)單元的作用。但是一旦這個(gè)過程發(fā)生破壞就會(huì)引發(fā)嚴(yán)重的疾病,，最典型的就是癌癥,，癌細(xì)胞可以無限制增殖，但是其細(xì)胞自我消化的能力卻是非常緩慢乃至停滯的,。
眾所周知,，調(diào)節(jié)細(xì)胞生長的生長因子可以刺激機(jī)體中新蛋白質(zhì)的合成，進(jìn)而促進(jìn)細(xì)胞的生長和分裂,。近日,，來自麥吉爾大學(xué)的研究者首次揭示了,，為了獲得細(xì)胞蛋白質(zhì)合成所需的氨基酸的供給，生長因子可以通過調(diào)節(jié)/刺激作用來增加細(xì)胞中蛋白質(zhì)的破損,，從而來產(chǎn)生游離的氨基酸以產(chǎn)生新的蛋白質(zhì),。這種氨基酸的重復(fù)利用確保了細(xì)胞可以以最佳的狀態(tài)來適應(yīng)環(huán)境。相關(guān)研究成果刊登在了近日的國際雜志Journal of Biological Chemistry上,。
新研究發(fā)現(xiàn)的這個(gè)細(xì)胞過程,，就好比是我們要蓋房子，必須有充足的木材來作為原料,，以確保我們木材的可用以及持續(xù)性以免發(fā)生木材不夠用的情況,。通過研究大鼠的肝臟細(xì)胞，研究者揭示了生長因子可以促進(jìn)細(xì)胞酸化的作用,，這種酸化作用將會(huì)導(dǎo)致細(xì)胞中蛋白質(zhì)的分解并游離為氨基酸,，以保證細(xì)胞維持健康生長所必須的氨基酸。
這項(xiàng)研究或許為開發(fā)癌癥及糖尿病的療法提供幫助,，同時(shí)也指出了開發(fā)抵御某些疾病的新型藥物的前景,。（生物谷Bioon.com）
編譯自：Coordinated protein breakdown and synthesis: a key to healthy growth of cells
doi:10.1074/jbc.M112.352229
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Epidermal Growth Factor-induced Vacuolar (H+)-ATPase Assembly A ROLE IN SIGNALING VIA mTORC1 ACTIVATION*
Yanqing Xu‡,1, Amanda Parmar‡,1, Emmanuelle Roux‡, Alejandro Balbis‡, Victor Dumas‡, Stephanie Chevalier§ and Barry I. Posner‡,2
Using proteomics and immunofluorescence, we demonstrated epidermal growth factor (EGF) induced recruitment of extrinsic V1 subunits of the vacuolar (H+)-ATPase (V-ATPase) to rat liver endosomes. This was accompanied by reduced vacuolar pH. Bafilomycin, an inhibitor of V-ATPase, inhibited EGF-stimulated DNA synthesis and mammalian target of rapamycin complex 1 (mTORC1) activation as indicated by a decrease in eukaryotic initiation factor 4E-binding 1 (4E-BP1) phosphorylation and p70 ribosomal S6 protein kinase (p70S6K) phosphorylation and kinase activity. There was no corresponding inhibition of EGF-induced Akt and extracellular signal-regulated kinase (Erk) activation. Chloroquine, a neutralizer of vacuolar pH, mimicked bafilomycin effects. Bafilomycin did not inhibit the association of mTORC1 with Raptor nor did it affect AMP-activated protein kinase activity. Rather, the intracellular concentrations of essential but not non-essential amino acids were decreased by bafilomycin in EGF-treated primary rat hepatocytes. Cycloheximide, a translation elongation inhibitor known to augment intracellular amino acid levels, prevented the effect of bafilomycin on amino acids levels and completely reversed its inhibition of EGF-induced mTORC1 activation. In vivo administration of EGF stimulated the recruitment of Ras homologue enriched in brain (Rheb) but not mammalian target of rapamycin (mTOR) to endosomes and lysosomes. This was inhibited by chloroquine treatment. Our results suggest a role for vacuolar acidification in EGF signaling to mTORC1.
