JAK2 activation in myeloproliferative neoplasms: a potential role for heterodimeric receptors.
The various roles and importance of JAK2 in cell signaling have been appreciated for some time. In 2005, a point mutation in JAK2 (JAK2-V617F) was identified in a number of neoplastic myeloproliferative disorders, ushering in a new era of JAK2 research. This discovery uncovered a new therapeutic target to treat these neoplasms and in turn possibly prevent their progression into cancer. A thorough understanding of the mechanism of JAK2-V617F-mediated activation will enhance our knowledge of how JAK2 contributes to these diseases. While mutationally activated, JAK2-V617F still requires homodimeric cytokine receptors to provide a scaffold upon which the JAK2 molecules trans-activate each other via phosphorylation. We have recently shown that in addition to homodimeric receptors, single components of heterodimeric cytokine receptors may substitute for homodimeric receptors in activation of this mutant JAK2. While mutations in homodimeric cytokine receptors have been found in JAK2-negative myeloproliferative neoplasms, it is possible that components of heterodimeric receptors also contribute to these disorders through aberrant expression or mutational activation.
Reuther
Gary W
GW
H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA. gary.reuther@moffitt.org
D004789:Enzyme Activation / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics*; D018121:Receptors, Cytokine / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism
C112441:IL27RA protein, human; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; C507924:JAK2 protein, human; D053614:Janus Kinase 2