Characterization of the role of the human granulocyte-macrophage colony-stimulating factor receptor � 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 (GMRa) and a common beta (bc) subunit. The intracel-lular 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 per-formed. 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 wer