| First Author | Chen J | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 9 | Pages | 5763-73 |
| PubMed ID | 19109256 | Mgi Jnum | J:147898 |
| Mgi Id | MGI:3842881 | Doi | 10.1074/jbc.M808197200 |
| Citation | Chen J, et al. (2009) A new isoform of interleukin-3 receptor {alpha} with novel differentiation activity and high affinity binding mode. J Biol Chem 284(9):5763-73 |
| abstractText | Interleukin-3 (IL-3) promotes both self-renewal and differentiation of early multipotential progenitors and is involved in inducible hematopoiesis in response to infections. Here we report new insights into these processes with the identification of a new isoform (SP2) of IL-3 receptor alpha (IL-3Ralpha), present in mouse and human hematopoietic cells, which lacks domain 1 of the full-length receptor (SP1). Binding assays with beta(IL-3) mutants showed that mouse SP2 uses a different high affinity binding mode to SP1, although both mouse and human SP2 and SP1 can stimulate IL-3-dependent growth. In IL-3-dependent differentiation models, human SP2 and SP1 gave differential effects on lineage commitment or self-renewal dependent on the cellular context, suggesting that different modes of ectodomain binding may modulate intracellular signaling. In a multipotential factor dependent cell-Paterson mix, the transcription factors C/EBPalpha and PU.1 and microRNAs miRNA-15a, -223, and -181a were up-regulated in cells undergoing SP2-supported differentiation compared with SP1-supported self-renewal. Similarly in M1 cells, SP2 promoted differentiation compared with SP1 and gave up-regulation of PU.1 and miRNA-155 and -223. These findings suggest that IL-3-promoted lineage commitment uses similar mechanisms to those of steady-state hematopoiesis. Both the SP1 and SP2 isoforms activated the Jak2/STAT5, Akt, and Erk1/2 signaling pathways in M1 cells, although the activation was more prolonged for the SP2 isoform. |
