THE CYTOPLASMIC DOMAIN OF STEM-CELL ANTIGEN CD34 IS ESSENTIAL FOR CYTOADHESION SIGNALING BUT NOT SUFFICIENT FOR PROLIFERATION SIGNALING

CD34 is widely used as a marker in the identification and purification of human hematopoietic stem and progenitor cells; however, its functi on within hematopoiesis is largely unknown. We have investigated the c ontribution of cytoplasmic domain of CD34 in cytoadhesion signaling an d proliferation signaling in hematopoietic cells. Engagement of partic ular determinants of CD34 by monoclonal antibodies leads to homotypic adhesiveness of the full-length CD34-transfected BaF3 cells: However, this homotypic adhesiveness is abrogated in BaF3 cells transfected wit h the truncated CD34 lacking the cytoplasmic domain. Cytoadhesion sign aling through the cytoplasmic domain of CD34 cannot be restored throug h that of erythropoietin receptor (EPOR) or granulocyte colony-stimula ting factor receptor (G-CSFR), suggesting that the cytoplasmic domain of CD34 is required for its signal transduction of cellular adhesion. In constrast, we show that replacing the cytoplasmic domain of EPOR or G-CSFR with that of CD34 abolished growth signal transduction in resp onse to EPO or G-CSF in the chimeric receptor-transfected BaF3, 32D, a nd FDCP1 cells. whereas the wild-type EPOR- or G-CSFR-transfected cell s responded to EPO or G-CSF growth signaling well. These results Sugge st that the cytoplasmic portion of CD34 may not contain the elements n ecessary to transduce a proliferative signal in hematopoietic cells. T hus. the function of CD34 in hematopoiesis is primarily oh hematopoiet ic cell adhesion. (C) 1998 by The American Society of Hematology.