Kolanus Waldemar
Laboratory of Molecular Immunology, Program Unit Molecular Immune and Cell Biology, LIMES (Life and Medical Sciences Bonn), University of Bonn, Bonn, Germany.
Immunol Rev. 2007 Aug;218:102-13. doi: 10.1111/j.1600-065X.2007.00542.x.
Members of the cytohesin protein family, a group of guanine nucleotide exchange factors for adenosine diphosphate ribosylation factor (ARF) guanosine triphosphatases, have recently emerged as important regulators of signal transduction in vertebrate and invertebrate biology. These proteins share a modular domain structure, comprising carboxy-terminal membrane recruitment elements, a Sec7 homology effector domain, and an amino-terminal coiled-coil domain that serve as a platform for their integration into larger signaling complexes. Although these proteins have a highly similar overall build, their individual biological functions appear to be at least partly specific. Cytohesin-1 had been identified as a regulator of beta2 integrin inside-out regulation in immune cells and was subsequently shown to be involved in mitogen-associated protein kinase signaling in tumor cell proliferation as well as in T-helper cell activation and differentiation. Cytohesin-3, which had been discovered to be strongly associated with T-cell anergy, was very recently described as an essential component of insulin signal transduction in Drosophila and in human and murine liver cells. Future work will aim to dissect the mechanistic details of the modes of action of the cytohesins as well as to define the precise roles of these versatile proteins in vertebrates at the genetic level.
细胞衔接蛋白家族的成员是一组针对二磷酸腺苷核糖基化因子（ARF）鸟苷三磷酸酶的鸟嘌呤核苷酸交换因子，最近已成为脊椎动物和无脊椎动物生物学中信号转导的重要调节因子。这些蛋白质具有模块化的结构域结构，包括羧基末端膜募集元件、Sec7同源效应结构域和氨基末端卷曲螺旋结构域，这些结构域作为它们整合到更大信号复合物中的平台。尽管这些蛋白质的整体结构高度相似，但它们各自的生物学功能似乎至少部分具有特异性。细胞衔接蛋白-1已被确定为免疫细胞中β2整合素外向内调节的调节因子，随后被证明参与肿瘤细胞增殖中的丝裂原相关蛋白激酶信号传导以及T辅助细胞的激活和分化。细胞衔接蛋白-3已被发现与T细胞无能密切相关，最近被描述为果蝇以及人类和小鼠肝细胞中胰岛素信号转导的重要组成部分。未来的工作旨在剖析细胞衔接蛋白作用模式的机制细节，并在基因水平上确定这些多功能蛋白质在脊椎动物中的精确作用。
