Scapini Patrizia, Pereira Shalini, Zhang Hong, Lowell Clifford A
Department of Laboratory Medicine, University of California, San Francisco, CA 94143-0451, USA.
Immunol Rev. 2009 Mar;228(1):23-40. doi: 10.1111/j.1600-065X.2008.00758.x.
Lyn is an Src family kinase present in B lymphocytes and myeloid cells. In these cell types, Lyn establishes signaling thresholds by acting as both a positive and a negative modulator of a variety of signaling responses and effector functions. Lyn deficiency in mice results in the development of myeloproliferation and autoimmunity. The latter has been attributed to the hyper-reactivity of Lyn-deficient B cells due to the unique role of Lyn in downmodulating B-cell receptor activation, mainly through phosphorylation of inhibitory molecules and receptors. Myeloproliferation results, on the other hand, from the enhanced sensitivity of Lyn-deficient progenitors to a number of colony-stimulating factors (CSFs). The hyper-sensitivity to myeloid growth factors may also be secondary to poor inhibitory receptor phosphorylation, leading to impaired recruitment/activation of tyrosine phosphatases and reduced downmodulation of CSF signaling responses. Despite these observations, the overall role of Lyn in the modulation of myeloid cell effector functions is much less well understood, as often both positive and negative roles of this kinase have been reported. In this review, we discuss the current knowledge of the duplicitous nature of Lyn in the modulation of myeloid cell signaling and function.
Lyn是一种存在于B淋巴细胞和髓系细胞中的Src家族激酶。在这些细胞类型中，Lyn通过作为多种信号反应和效应功能的正向和负向调节因子来建立信号阈值。小鼠中Lyn缺乏会导致骨髓增殖和自身免疫的发展。后者归因于Lyn缺陷型B细胞的高反应性，这是由于Lyn在下调B细胞受体激活中具有独特作用，主要是通过抑制性分子和受体的磷酸化。另一方面，骨髓增殖是由于Lyn缺陷型祖细胞对多种集落刺激因子（CSF）的敏感性增强。对髓系生长因子的超敏反应也可能继发于抑制性受体磷酸化不足，导致酪氨酸磷酸酶的募集/激活受损以及CSF信号反应的下调减少。尽管有这些观察结果，但Lyn在调节髓系细胞效应功能中的整体作用仍知之甚少，因为经常报道这种激酶的正向和负向作用。在这篇综述中，我们讨论了目前关于Lyn在调节髓系细胞信号传导和功能中的双重性质的知识。
