5 years ago

Interferon-{gamma} is a master checkpoint regulator of cytokine-induced differentiation [Developmental Biology]

Interferon-{gamma} is a master checkpoint regulator of cytokine-induced differentiation [Developmental Biology]
Anahita Nejatfard, Felicitas Bucher, Tianqing Zheng, Kyungmoo Yea, Hongkai Zhang, Zhao Zha, Richard A. Lerner

Cytokines are protein mediators that are known to be involved in many biological processes, including cell growth, survival, inflammation, and development. To study their regulation, we generated a library of 209 different cytokines. This was used in a combinatorial format to study the effects of cytokines on each other, with particular reference to the control of differentiation. This study showed that IFN-γ is a master checkpoint regulator for many cytokines. It operates via an autocrine mechanism to elevate STAT1 and induce internalization of gp130, a common component of many heterodimeric cytokine receptors. This targeting of a receptor subunit that is common to all members of an otherwise diverse family solves the problem of how a master regulator can control so many diverse receptors. When one adds an autocrine mechanism, fine control at the level of individual cells is achieved.

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