Human interleukin‐4 receptor signaling requires sequences contained within two cytoplasmic regions

The signaling pathway used by the murine or human interleukin‐4 receptor (WL‐4R) has not been elucidated so far. As an approach to mapping the cytoplasmic regions of the hIL‐4R that are essential for mediating the biological response upon IL‐4 binding we have cloned and expressed the wild‐type ML‐4R and several cytoplasmic deletion mutants in the murine IL‐3‐dependent pro‐B cell line BA/F3. Transfection of the wild‐type hIL‐4R conferred the ability on BA/F3 cells to proliferate in a dose‐dependent way when treated with human EL‐4. The analysis of six deletion mutants indicated that the signaling function of the hIL‐4R depends on sequences within two discontinuous regions that are located between amino acid He233 and Ser365 and Thr462 and Ala580 of the intracy toplasmic domain. The deletion of either of these regions totally abrogated IL‐4‐inducible growth. The relevance of our data is discussed in relation to the results obtaind from similar studies with other members of the hematopoietin receptor superfamily.

[1]  A. Miyajima,et al.  Critical cytoplasmic domains of the common beta subunit of the human GM‐CSF, IL‐3 and IL‐5 receptors for growth signal transduction and tyrosine phosphorylation. , 1992, The EMBO journal.

[2]  John Calvin Reed,et al.  Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell line. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  H. Shibuya,et al.  c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[4]  K. Yasukawa,et al.  Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Perlmutter,et al.  Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association , 1991, Science.

[6]  O. Majdic,et al.  Interleukin 4 promotes expression of mast cell ICAM-1 antigen. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[7]  T. Hirano,et al.  Molecular cloning and expression of an IL-6 signal transducer, gp130 , 1990, Cell.

[8]  K. Arai,et al.  Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  C. March,et al.  Expression cloning of a human granulocyte colony-stimulating factor receptor: a structural mosaic of hematopoietin receptor, immunoglobulin, and fibronectin domains , 1990, The Journal of experimental medicine.

[10]  C. March,et al.  Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily , 1990, The Journal of experimental medicine.

[11]  J. Bazan,et al.  Haemopoietic receptors and helical cytokines. , 1990, Immunology today.

[12]  T. Taniguchi,et al.  A restricted cytoplasmic region of IL-2 receptor β chain is essential for growth signal transduction but not for ligand binding and internalization , 1989, Cell.

[13]  T. Taniguchi,et al.  Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. , 1989, Science.

[14]  M. Steinmetz,et al.  IL3-dependent mouse clones that express B-220 surface antigen, contain ig genes in germ-line configuration, and generate B lymphocytes in vivo , 1985, Cell.

[15]  J. Calvo,et al.  Measurement of specific radioactivities in labelled hormones by self-displacement analysis. , 1983, The Biochemical journal.