The interleukin-4 receptor: signal transduction by a hematopoietin receptor.
Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.
Keegan
A D
AD
Laboratory of Immunology, NIAID, National Institutes of Health, Bethesda, MD 20892.
Pierce
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000378:metabolism / Q000502:physiology*; D008961:Models, Structural; D008969:Molecular Sequence Data; D005810:Multigene Family; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine