Cystic fibrosis (CF) is a lethal inherited disease produced by mutations in the gene encoding the CFTR chloride channel. Loss of function in the CFTR gene is associated with a not much noticed increased expression and activity of the non-receptor protein-tyrosine kinase c-Src. CF is therefore the result from the loss of CFTR chloride transport function and its consequences, including a chronic and excessive c-Src signaling. On the other hand, c-Src, encoded by the SRC gene, is involved in diverse signaling mechanisms that regulate key cellular functions such as cell proliferation, apoptosis, oxidative stress, inflammation, and innate immunity. These c-Src-regulated cellular functions are also affected in CF; however, studies exploring a direct role of c-Src in the regulation of these cellular functions in CF are yet scarce and often controversial. Here we describe the c-Src regulation and functions, with emphasis in those altered in CF, and describe the role of CFTR as a "signaling molecule" that negatively modulates c-Src expression and activity. It is also discussed the emerging role of intracellular Cl- and IL-1β as intermediate signaling effectors between CFTR and c-Src.

中文翻译：

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c-Src及其在囊性纤维化中的作用。

囊性纤维化（CF）是一种致命的遗传性疾病，由编码CFTR氯化物通道的基因突变产生。CFTR基因功能的丧失与非受体蛋白酪氨酸激酶c-Src的表达和活性增加无关。因此，CF是CFTR氯化物转运功能丧失及其后果（包括长期和过度的c-Src信号转导）的结果。另一方面，由SRC基因编码的c-Src参与了多种信号传导机制，这些机制调节关键的细胞功能，例如细胞增殖，凋亡，氧化应激，炎症和先天免疫。这些c-Src调控的细胞功能在CF中也会受到影响；然而，探索c-Src在CF中调节这些细胞功能中直接作用的研究仍然很少，而且经常引起争议。在这里，我们描述了c-Src的调控和功能，着重介绍了CF中的变化，并描述了CFTR作为“信号分子”的作用，它负面地调节了c-Src的表达和活性。还讨论了细胞内Cl-和IL-1β作为CFTR和c-Src之间的中间信号转导效应子的新兴作用。