title: Activation of the Jak3 pathway and myeloid differentiation.
abstract: Although the role of Jak3 in lymphoid development has been well-characterized, increasing evidence demonstrates that activation of the Jak3 pathway plays an important role in myeloid differentiation as well. Overexpression of Jak3 in murine myeloid 32Dcl3 cells has been shown to result in an acceleration of granulocytic differentiation induced by G-CSF. Early onset of G1 cell cycle arrest along with upregulation of the cyclin dependent kinase inhibitor p27Kip1 and downregulation of Cdk2, Cdk4, Cdk6, and Cyclin E has also been observed in Jak3-overexpressing 32Dcl3 cells. In addition, Jak3 overexpression in normal mouse bone marrow cells results in accelerated granulocytic and monocytic differentiation in response to GM-CSF, while pharmacological inhibition of Jak3 results in a block to GM-CSF-induced colony formation in normal mouse bone marrow cells. Jak3 is unique among the members of the Jak kinase family in that it is inducibly expressed and is a target for regulation at the level of transcription. Recent studies have demonstrated that upregulation of Jak3 during myeloid differentiation is achieved through the cooperative action of Sp1 and STAT3, consistent with evidence indicative of a crucial role for STAT3 in myeloid differentiation. These results suggest that cytokine-inducible activation of Jak3 plays a critical role in integrating the processes of growth arrest and differentiation of myeloid cells.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadephia, PA 19140, USA.
authors.forename: James K
authors.initials: JK
authors.lastname: Mangan
authors.forename: E Premkumar
authors.initials: EP
authors.lastname: Reddy
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004789:Enzyme Activation; D006801:Humans; D053616:Janus Kinase 3; D022423:Myeloid Cells / Q000166:cytology* / Q000201:enzymology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3