細(xì)胞外的信號(hào)通過(guò)蛋白與蛋白和蛋白與配體的作用由細(xì)胞表面?zhèn)魉偷郊?xì)胞核。細(xì)胞通過(guò)特殊蛋白質(zhì)如激素、細(xì)胞因子或其它分子傳感器而持續(xù)感受外界環(huán)境變化并作出反應(yīng)。這些信號(hào)分子通過(guò)與細(xì)胞受體結(jié)合發(fā)揮作用,將信息傳導(dǎo)到細(xì)胞核中,在那里特殊基因由于外界環(huán)境變化而被激活。信號(hào)從細(xì)胞表面?zhèn)鞯郊?xì)胞核是經(jīng)由"第二信息子"完成的,這種信息子可以是胞內(nèi)蛋白或小分子如環(huán)狀A(yù)MP、肌醇磷酸鹽或鈣離子。信號(hào)傳導(dǎo)系統(tǒng)的一個(gè)例子是細(xì)胞對(duì)血液中葡萄糖水平的反應(yīng)。通過(guò)葡萄糖與細(xì)胞受體結(jié)合感受到高水平,該信號(hào)最終傳到細(xì)胞核中并激活包括胰島素基因在內(nèi)的特定基因,然后胰島素被合成,并離開細(xì)胞,起到降低葡萄糖水平的作用。信號(hào)傳導(dǎo)對(duì)于制藥業(yè)非常重要,因?yàn)楹芏嗉膊〉漠惓7磻?yīng)是由于細(xì)胞或構(gòu)成信號(hào)傳導(dǎo)的蛋白質(zhì)突變?cè)斐傻摹@影ㄉ婕爸笇?dǎo)基因成長(zhǎng)和分裂的成長(zhǎng)因子和胞內(nèi)蛋白。任何這些分子的變化都會(huì)導(dǎo)致不可控制的細(xì)胞生長(zhǎng)。超過(guò)50%的人類腫瘤的發(fā)現(xiàn)是通過(guò)二個(gè)胞內(nèi)信號(hào)通道識(shí)別的,即:JAK/STAT和p53/ras通道。
The transmission of an extracellular signal from the surface of the cell to the nucleus by a relay of protein-protein and protein-ligand interactions. Cells continuously sense and respond to their changing environmental conditions via specialized proteins such as the hormones, cytokines, or other molecular sensors. These signal molecules exhibit their effects by binding to cellular receptors after which their message (or signal) gets “transduced” to the nucleus of the cell, where specific genes are activated in response to the alteration in the environmental conditions. The relaying of the signal from the cell surface to the nucleus is mediated by “second messengers,” which can be intracellular proteins or small molecules such as cyclic AMP, inositol phosphate, or calcium ions. An example of a signal transduction pathway is the cell’s response to glucose levels in the bloodstream. High levels are sensed by the binding of glucose to a cellular receptor, and a signal is transduced which eventually leads to the nucleus to activate certain genes including the insulin gene. Insulin is then synthesized, leaves the cell, and acts to lower glucose levels. Signal transduction is of critical importance to the pharmaceutical industry since many disease states are due to the aberrant responses of cells to external agents, or due to mutations to proteins that form the signal transduction machinery. Examples involve the growth factors and the intracellular proteins involved in signaling the genes for cell growth and division. Changes to any of these molecules can result in uncontrolled cell growth. Over 50% of human cancers have been identified as resulting from just two intracellular signaling pathways: the JAK/STAT and p53/ras pathways.