Interleukin-4 receptor signaling and its binding mechanism

A therapeutic insight from inhibitors tool box

Zaheer Ul-Haq, Sehrish Naz, Osman Mesaik Mohammed Ahmed Hassan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Studies on Interlukin-4 (IL-4) disclosed great deal of information about its various physiological and pathological roles. All these roles depend upon its interaction and signaling through either type-I (IL-4Rα/common γ-chain) or type-II (IL-4Rα/IL-13Rα) receptors. Another cytokine, IL-13, shares some of the functions of IL-4, because both cytokines use a common receptor subunit, IL-4Rα. Here in this review, we discuss the structural details of IL-4 and IL-4Rα subunit and the structural similarities between IL-4 and IL-13. We also describe detailed chemistry of type-I and type-II receptor complexes and their signaling pathways. Furthermore, we elaborate the strength of type-II hetero dimer signals in response to IL-4 and IL-13. These cytokines are prime players in pathogenesis of allergic asthma, allergic hypersensitivity, different cancers, and HIV infection. Recent advances in the structural and binding chemistry of these cytokines various types of inhibitors were designed to block the interaction of IL-4 and IL-13 with their receptor, including several IL-4 mutant analogs and IL-4 antagonistic antibodies. Moreover, different targeted immunotoxins, which is a fusion of cytokine protein with a toxin or suicidal gene, are the new class of inhibitors to prevent cancer progression. In addition few small molecular inhibitors such as flavonoids have also been developed which are capable of binding with high affinity to IL-4Rα and, therefore, can be very effective in blocking IL-4-mediated responses.

Original languageEnglish
JournalCytokine and Growth Factor Reviews
DOIs
Publication statusAccepted/In press - 5 Jan 2016
Externally publishedYes

Fingerprint

Interleukin-4 Receptors
Interleukin-13
Cytokines
Therapeutics
Immunotoxins
Flavonoids
Interleukin-4
Dimers
HIV Infections
Neoplasms
Hypersensitivity
Fusion reactions
Asthma
Genes
Antibodies
Proteins

Keywords

  • Allergic asthma
  • Antagonistic antibodies
  • Cancers
  • IL-4 mutant analogs
  • Immunotoxins
  • Interleukin-4

ASJC Scopus subject areas

  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Immunology and Allergy
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Interleukin-4 receptor signaling and its binding mechanism : A therapeutic insight from inhibitors tool box. / Ul-Haq, Zaheer; Naz, Sehrish; Mohammed Ahmed Hassan, Osman Mesaik.

In: Cytokine and Growth Factor Reviews, 05.01.2016.

Research output: Contribution to journalArticle

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