Phosphorylation of Jak2 on Ser 523 InhibitsJak2-Dependent Leptin ReceptorSignaling

Author:

Ishida-Takahashi Ryoko1,Rosario Felicia2,Gong Yusong1,Kopp Keely1,Stancheva Zlatina1,Chen Xiaohong2,Feener Edward P.2,Myers Martin G.1

Affiliation:

1. Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109

2. Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215

Abstract

ABSTRACT The leptin receptor, LRb, and other cytokine receptors are devoid of intrinsic enzymatic activity and rely upon the activity of constitutively associated Jak family tyrosine kinases to mediate intracellular signaling. In order to clarify mechanisms by which Jak2, the cognate LRb-associated Jak kinase, is regulated and mediates downstream signaling, we employed tandem mass spectroscopic analysis to identify phosphorylation sites on Jak2. We identified Ser 523 as the first-described site of Jak2 serine phosphorylation and demonstrated that this site is phosphorylated on Jak2 from intact cells and mouse spleen. Ser 523 was highly phosphorylated in HEK293 cells independently of LRb-Jak2 activation, suggesting a potential role for the phosphorylation of Ser 523 in the regulation of LRb by other pathways. Indeed, mutation of Ser 523 sensitized and prolonged signaling by Jak2 following activation by the intracellular domain of LRb. The effect of Ser 523 on Jak2 function was independent of Tyr 570 -mediated inhibition. Thus, the phosphorylation of Jak2 on Ser 523 inhibits Jak2 activity and represents a novel mechanism for the regulation of Jak2-dependent cytokine signaling.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

Cited by 51 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3