Tyrosine phosphorylation activates the enzyme activity of t but also the recruitment of downstream signaling proteins PS-341 Bortezomib By comparison Change in the conformation and the creation of binding sites for proteins With Src homology 2-Dom NEN. In principle, PTK , depending on their cellular Re localization. Receptor are transmembrane receptors with intrinsic Kinasedom Ne the intracellular Ren part of the receptor. Myelofibrosis is a disorder of the bone marrow by a berm Characterizes owned production of collagen and reticulin fibers. Although fibrosis is the result of many conditions, h Dermatological and not h Dermatological 1 MF term is h Frequently used to refer to the prime Re MF 2 and adversely Chtigte development of two more Hnlichen classic Philadelphia chromosome negative myeloproliferative diseases either: Polyzyth mie vera and essential Thrombozyth mie. 3 According to epidemiological studies, can k 4 9 the incidence of PMF as high as 1.5 per 100,000. Other studies10 14 show that by the end of the second decade after diagnosis PV or CUDC-101 ET, up to 10% to 15% of F Lle k Can secondary Re MF become. In MF appearing fibrotic Ver Changes such as cytokines stimulated reactions multilineage clonal cells proliferation.15 suffered 21 The clinical symptoms are due to splenomegaly MF hematopoietic h Extramedull Re ESR, leukocytosis and thrombocytosis, with a Pr Disposition for thrombotic events by clonal cell proliferation Haupt Chlich granulocytes and megakaryocytes, cytopenias, a subsequent finding that worsens with the progression of fibrosis and symptom caused my constitutional, probably due to abnormal levels of circulating cytokines. In the last ten years, the r Janus kinases in the intracellular Ren pathways myeloproliferative neoplasms the attention of many researchers. JAK kinases are non-receptor tyrosine in the transmission of intracellular cytokine and growth by Involved re signals induced. Approximately 50% of patients with this mutation PMF JAK2V617F Gain rkungsfunktion, Leading to a signal transmitter activated JAK fa One constitutive and activator of transcription pathway.22, 23 in turn, the active JAK STAT pathway Including the transcription of many genes, such as cytokines, fibrogenic factors and angiogenic factors Lich a plurality of pro-and anti-apoptotic proliferative products.24 29 above the per cent production of inflammatory cytokines k Jakstat activation may be contributing 30 creates a vicious circle. Among the patients with MF, approximately 5% are JAK2V617F negative, but happier t gain of function mutation in the receptor gene thrombopo Retina, which then caused cytokine independent JAK-dependent STAT activation.31, 32, another small group of patients with MF, none of these mutations, however, are 34 different mutations with constitutive activation of JAK2 connected. Au Addition k Can patients with MF in the absence of any identified mutation site often exhibit hyperactive JAK2. JAK1 plays a r In the MF: A recent study30 showed JAK1 Hyperaktivit t in patients with MF, probably as a result of over stimulation of cytokines. Overall, these data indicate that JAK1 and JAK2 important pieces of the puzzle that represents the molecular pathogenesis of MF.