Characterization of the Role of the Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor α Subunit in the Activation of JAK2 and STAT5

摘要: The high-affinity human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR) consists of an alpha (GMRalpha) and a common beta (betac) subunit. intracellular domain betac has been extensively characterized shown to be critical for the activation both JAK/STAT MAP kinase pathways. function GMRalpha, however, is not as well characterized. To determine role this in GMR signaling, extensive structure-function analysis was performed. Truncation mutants alpha362, alpha371, alpha375 were generated, site-directed alphaVQVQ alphaVVVV. Although alpha375beta, alphaVQNQbeta, alphaVVVVbeta stimulated proliferation response GM-CSF, truncation alpha362beta alpha371beta incapable transducing proliferative signal. In addition, alpha371 alphaVVVV expressed at markedly reduced levels, indicating importance residues 372 374 proper protein expression. More importantly, we show that GMRalpha plays direct pathway, electrophoretic mobility shift assays (EMSA) indicate play determining STAT5 DNA binding complex activated by GMR. Thus, important pathway stabilization.