Silvennoinen O
Institute of Medical Technology, University of Tampere, Department of Clinical Microbiology, Tampere University Hospital, Finland.
Ann Med. 1997 Dec;29(6):519-29. doi: 10.3109/07853899709007476.
Extracellular signals, such as cytokines and foreign antigens, regulate the development and activation of haematopoietic cells through receptor-mediated transcriptional responses. Investigation of the biochemical events that transduce receptor activation to intracellular signal transduction have revealed a general mechanism for both the antigen receptor and the cytokine receptor nuclear signalling. Receptor stimulation is coupled to down-stream signalling cascades through activation of cytoplasmic tyrosine kinases but both receptor types utilize distinct signalling proteins. Antigen receptors employ protein tyrosine kinases of the Src, Syk, and Tec families which phosphorylate and activate cytoplasmic signalling proteins leading to activation of NF-AT, AP-1 and NF-kappaB transcription factors, while the principal signal transducers for cytokine receptors are the Jak tyrosine kinases and Stat transcription factors. The molecular basis for several immune and haematological disorders has been characterized during the last few years and they have been found to be caused by defects in various signalling proteins. In this review the aetiology of immune and haematological disorders is discussed in the light of the recent developments in signal transduction.
细胞外信号，如细胞因子和外来抗原，通过受体介导的转录反应来调节造血细胞的发育和激活。对将受体激活转导至细胞内信号转导的生化事件的研究揭示了抗原受体和细胞因子受体核信号传导的一般机制。受体刺激通过细胞质酪氨酸激酶的激活与下游信号级联反应相偶联，但这两种受体类型利用不同的信号蛋白。抗原受体采用Src、Syk和Tec家族的蛋白酪氨酸激酶，这些激酶磷酸化并激活细胞质信号蛋白，导致NF-AT、AP-1和NF-κB转录因子的激活，而细胞因子受体的主要信号转导分子是Jak酪氨酸激酶和Stat转录因子。在过去几年中，已经阐明了几种免疫和血液学疾病的分子基础，并且发现它们是由各种信号蛋白的缺陷引起的。在这篇综述中，根据信号转导的最新进展讨论了免疫和血液学疾病的病因。
