Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor.
IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with Stat6 DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R.
Ryan
J J
JJ
National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA.
McReynolds
L J
LJ
Keegan
A
A
Wang
L H
LH
Garfein
E
E
Rothman
P
P
Nelms
K
K
Paul
W E
WE
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics* / Q000494:pharmacology; D016393:Lymphoma, B-Cell; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000494:pharmacology; D017455:Receptors, IgE / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D019948:Receptors, Interleukin-4; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000032:analysis
D015703:Antigens, CD; D018970:Insulin-Like Growth Factor Binding Protein 1; D015221:Potassium Channels; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D014443:Tyrosine