MOLECULAR-CLONING OF 2 ISOFORMS OF A RECEPTOR FOR THE HUMAN HEMATOPOIETIC CYTOKINE INTERLEUKIN-11

Interleukin-11 (IL-11) is a stromal cell-derived cytokine with multipl e biologic activities on lymphohematopoietic cells. It belongs to a fa mily of pleiotropic and redundant cytokines that use the gp130 transdu cing subunit in their high affinity receptors. By amplifying human cDN A libraries with oligonucleotide primers corresponding to the conserve d WSXWS moth found in the hematopoietic cytokine receptor family, a no vel cytokine receptor cDNA was identified that, based on high (82%) se quence homology with the recently cloned murine IL-11 receptor, appear s to encode the human IL-11 receptor. This receptor is a 422-amino aci d protein containing a signal peptide followed by extracellular, trans membrane, and cytoplasmic domains. The extracellular region has a two- domain structure homologous to those of the IL-6 and ciliary neurotrop hic factor (CNTF) receptors: an immunoglobulin-like domain and a cytok ine receptor-like domain. In addition, an isoform of the human IL-11 r eceptor that lacks the cytoplasmic domain was also identified. In agre ement with the pleiotropic effects of IL-11 on different hematopoietic lineages and bone cells, IL-11 receptor transcripts were found to be expressed by the myelogenous leukemia cell line K562, the megakaryocyt ic leukemia cell line Mo7E, the erythroleukemia cell line TF1, and the osteosarcoma cell lines MG-63 and Saos-2. (C) 1995 by The American So ciety of Hematology.