gp130 and the IL-6 family of cytokines

Signaling mechanisms and thrombopoietic activities

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

gp130 is a common signal transducing component of the functional receptor complexes for the interleukin (IL)-6 family of cytokines, ie, IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1. These cytokines exhibit pleiotropic biological activities in, for instance, immune, hematopoietic, and neural systems, and function in a redundant manner owing to the shared usage of gp130. Thrombopoiesis is regulated by a variety of polypeptide factors including some from the IL-6 family. A polypeptide that has the most potent thrombopoietic activity among the thus far identified molecules is thrombopoietin (TPO). TPO exerts its biological functions through its cognate receptor, c-MPL, that interestingly is classified into the hematopoietic cytokine receptor family in which gp130 also belongs. Although each member of the IL-6 family as well as TPO signals through the distinct receptor complex, the underlying signaling mechanism is similar in each case: the first event after cytokine stimulation is dimerization of a respective set of receptor components, and activation of receptor-associated tyrosine kinases in the janus kinase (JAK) family then follows. Activation of JAK kinases is the pivotal step to initiate downstream cytoplasmic signaling cascades involving signal transducer and activator of transcription transcription factors and mitogen activated protein kinase. In this article, we focus on gp130-mediated cytokine signal transduction by comparing that mediated by c-MPL.

Original languageEnglish
Pages (from-to)210-221
Number of pages12
JournalSeminars in Hematology
Volume35
Issue number3
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Thrombopoietin
Interleukin-6
Cytokines
Janus Kinases
Oncostatin M
Interleukin-11
Ciliary Neurotrophic Factor
Thrombopoiesis
Leukemia Inhibitory Factor
Interleukin-6 Receptors
Hematopoietic System
Peptides
Cytokine Receptors
Receptor Protein-Tyrosine Kinases
Dimerization
Mitogen-Activated Protein Kinases
Transducers
Signal Transduction
Transcription Factors
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

gp130 and the IL-6 family of cytokines : Signaling mechanisms and thrombopoietic activities. / Nakashima, Kinichi; Taga, T.

In: Seminars in Hematology, Vol. 35, No. 3, 1998, p. 210-221.

Research output: Contribution to journalReview article

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