JAK2是一種非受體酪氨酸激酶,，通過誘導(dǎo)胞質(zhì)信號級聯(lián)來調(diào)控各種不同細(xì)胞過程?，F(xiàn)在,，Dawson等人報告了JAK2的一個以前不知道的核功能。由JAK2催化的組蛋白H3的酪氨酸磷酸化,，會導(dǎo)致HP1-阿爾法與染色質(zhì)的結(jié)合被破壞,，并導(dǎo)致基因表達(dá)的變化。人們對這一發(fā)現(xiàn)之所以特別感興趣,，是因為JAK2抑制因子正在接受治療骨髓性白血病的臨床試驗,，在這種白血病中JAK2失控。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 461, 819-822 (8 October 2009) | doi:10.1038/nature08448
JAK2 phosphorylates histone H3Y41 and excludes HP1from chromatin
Mark A. Dawson1,2,4, Andrew J. Bannister3,4, Berthold G?ttgens1, Samuel D. Foster1, Till Bartke3, Anthony R. Green1,2,4 & Tony Kouzarides3,4
1 Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK
2 Department of Haematology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK
3 Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
4 These authors contributed equally to this work.
Correspondence to: Anthony R. Green1,2,4Tony Kouzarides3,4 Correspondence and requests for materials should be addressed to A.R.G. or T.K.
Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies1, 2, 3, 4, 5, 6. JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signalling cascades. Here we show that human JAK2 is present in the nucleus of haematopoietic cells and directly phosphorylates Tyr 41 (Y41) on histone H3. Heterochromatin protein 1 (HP1), but not HP1, specifically binds to this region of H3 through its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this binding. Inhibition of JAK2 activity in human leukaemic cells decreases both the expression of the haematopoietic oncogene lmo2 and the phosphorylation of H3Y41 at its promoter, while simultaneously increasing the binding of HP1 at the same site. &Tgr;hese results identify a previously unrecognized nuclear role for JAK2 in the phosphorylation of H3Y41 and reveal a direct mechanistic link between two genes, jak2 and lmo2, involved in normal haematopoiesis and leukaemia
