Erythroid molecular cascades involving the tyrosine kinase Lyn

成熟的红血球和白血球由成人骨髓中的造血干细胞发育而来。红细胞的产生主要受促红细胞生成素(EPO)激素的控制。重组形式的这种激素的可获得性有助于治疗由肾功能衰竭、恶性肿瘤和艾滋病引起的多种形式的贫血。在此之前，我们已经确定LYN蛋白必须存在于原始红细胞内，才能使EPO刺激它们成为成熟的功能细胞。最近，我们已经证明，缺乏LYN基因的小鼠的红细胞会出现严重问题。我们已经在红细胞中发现了几个与LYN相互作用的分子。我们已经证明了一种名为CBP的分子对单个红细胞中的EPO功能很重要，现在我们计划在整个动物中研究它的功能。我们已经证明了一种名为Arp的新分子对红细胞发育非常重要。这种蛋白质进出细胞核(储存DNA的地方)，可能在调节红细胞所需的基因方面发挥重要作用。第三个基因(AFAPbeta)也是新的，与另一个名为AFAP-110的基因密切相关，该基因可以对细胞结构产生影响。由于红细胞在发育过程中必须显著收缩，因此AFAPbeta对红细胞结构的作用也将被研究。从这些实验中，我们应该更好地了解红细胞的产生是如何被控制的，以及红细胞疾病(如贫血)是如何发生的。

Mature red and white cells develope from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functional cells. Recently, we have demonstrated that mice lacking the Lyn gene develope major problems with their red blood cells. We have identified several molecules which interact with Lyn in red blood cells. We have shown that a molecule called Cbp is important for Epo function in individual red blood cells and now we plan to investigate its function in whole animals. We have shown that a new molecule called Arp is important for red blood cell development. This protein moves in and out of the nucleus (where DNA is stored) and may be important in the regulation of genes needed for red blood cells. The third gene (AFAPbeta) is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Since red blood cells have to shrink considerably during their development, the role of AFAPbeta on red blood cell structure will also be investigated. From these experiments we should develop a much better understanding of how the production of red blood cells is controlled and how diseases of red blood cells (such as anaemia) occur.