Characterization of the Role of the Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor a Subunit in the Activation of JAK2 and STAT5
نویسندگان
چکیده
The high-affinity human granulocyte-macrophage colonystimulating factor (GM-CSF) receptor (GMR) consists of an alpha (GMRa) and a common beta (bc) subunit. The intracellular domain of bc has been extensively characterized and has been shown to be critical for the activation of both the JAK/STAT and MAP kinase pathways. The function of the intracellular domain of GMRa, however, is not as well characterized. To determine the role of this domain in GMR signaling, an extensive structure-function analysis was performed. Truncation mutants a362, a371, and a375 were generated, as well as the site-directed mutants aVQVQ and aVVVV. Although a375b, aVQNQb, and aVVVVb stimulated proliferation in response to human GM-CSF, the truncation mutants a362b and a371b were incapable of transducing a proliferative signal. In addition, both a371 and aVVVV were expressed at markedly reduced levels, indicating the importance of residues 372 to 374 for proper protein expression. More importantly, we show that GMRa plays a direct role in the activation of the JAK/STAT pathway, and electrophoretic mobility shift assays (EMSA) indicate that both GMRa and bc play a role in determining the STAT5 DNA binding complex activated by the GMR. Thus, the intracellular domain of the human GMRa is important for activation of the JAK/STAT pathway and protein stabilization. r 1998 by The American Society of Hematology.
منابع مشابه
Characterization of the role of the human granulocyte-macrophage colony-stimulating factor receptor alpha subunit in the activation of JAK2 and STAT5.
The high-affinity human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR) consists of an alpha (GMRalpha) and a common beta (betac) subunit. The intracellular domain of betac has been extensively characterized and has been shown to be critical for the activation of both the JAK/STAT and MAP kinase pathways. The function of the intracellular domain of GMRalpha, however, is...
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