Sharing of receptor subunits and signal transduction pathway between the IL-4 and IL-13 receptor system.
In this review, we summarize the subunit structure of the interleukin (IL)-4 and IL-13 receptor system and the molecular mechanism of signals through the cytokine receptor systems. We have demonstrated that two different forms of IL-4R exist, classical and alternative. Classical IL-4R is predominantly expressed in hematopoietic cells and consists of IL-4R p140 (beta) and IL-2R gamma (gamma c) chains. The alternative form of IL-4R is predominantly expressed in nonhematopoietic cells and consists of IL-4R beta and IL-13R alpha' chains. Moreover, the alternative form of IL-4R is also used as a functional component in the IL-13R complex. For signal transduction through IL-4R and IL-13R, we have demonstrated that in nonhematopoietic cells, Janus protein tyrosine kinase (JAK) 2 is phosphorylated and activated instead of JAK3 tyrosine kinase. While JAK3 is required for signal transducer and activator of transcription-6 (STAT6) activation in hematopoietic cells, we recently demonstrated that in nonhematopoietic cells JAK2 is required for STAT6 activation for the alternative form of IL-4R. Thus, a major difference exists between hematopoietic and nonhematopoietic cells with regard to structure and signal transduction through the IL-4R and IL-13R systems.
Murata
T
T
First Department of Internal Medicine, School of Medicine, Yokohama City University, Japan.
Taguchi
J
J
Puri
R K
RK
Mohri
H
H
D006413:Hematopoietic System / Q000166:cytology / Q000201:enzymology; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000737:chemistry; D009928:Organ Specificity; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin / Q000737:chemistry / Q000502:physiology*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000737:chemistry / Q000502:physiology*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000502:physiology
D018793:Interleukin-13; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D015534:Trans-Activators; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; D053614:Janus Kinase 2; D053616:Janus Kinase 3