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	The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury
	Vozdek, Roman1,2; Long, Yong1,2,3; Ma, Dengke K.1,2
刊名	SCIENCE SIGNALING
	2018-10-02
卷号	11期号:550页码:12
ISSN号	1945-0877
DOI	10.1126/scisignal.aat0138
通讯作者	Ma, Dengke K.(dengke.ma@ucsf.edu)
英文摘要	Inadequate tissue oxygen, or hypoxia, is a central concept in the pathophysiology of ischemic disorders and cancer. Hypoxia promotes extracellular matrix (ECM) remodeling, cellular metabolic adaptation, and cancer cell metastasis. To discover new pathways through which cells respond to hypoxia, we performed a large-scale forward genetic screen in Caenorhabditis elegans and identified a previously uncharacterized receptor tyrosine kinase named HIR-1. Loss of function in hir-1 phenocopied the impaired ECM integrity associated with hypoxia or deficiency in the oxygen-dependent dual oxidase, heme peroxidases, or cuticular collagens involved in ECM homeostasis. Genetic suppressor screens identified NHR-49 and MDT-15 as transcriptional regulators downstream of HIR-1. Furthermore, hir-1 mutants showed defects in adapting to and recovering from prolonged severe hypoxia. We propose that C. elegans HIR-1 coordinates hypoxia-inducible factor-independent responses to hypoxia and hypoxia-associated ECM remodeling through mechanisms that are likely conserved in other organisms.
资助项目	NIH[R01GM117461] ; NIH[R00HL116654] ; American Diabetes Association grant[1-16-IBS-197] ; Pew Scholar Award ; Alfred P. Sloan Foundation Fellowship ; Packard Fellowship in Science and Engineering ; Larry L. Hillblom start-up grant ; Larry L. Hillblom fellowship
WOS关键词	NEMATODE CAENORHABDITIS-ELEGANS ; C-ELEGANS ; OXYGEN DEPRIVATION ; STRESS-RESPONSE ; GENE ONTOLOGY ; GROWTH-FACTOR ; HYDROXYLASE ; CUTICLE ; CANCER ; PROLYL
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号	WOS:000446086600002
资助机构	NIH ; NIH ; NIH ; NIH ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; NIH ; NIH ; NIH ; NIH ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; NIH ; NIH ; NIH ; NIH ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; NIH ; NIH ; NIH ; NIH ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; American Diabetes Association grant ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Pew Scholar Award ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Alfred P. Sloan Foundation Fellowship ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Packard Fellowship in Science and Engineering ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom start-up grant ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship ; Larry L. Hillblom fellowship
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/29280]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
通讯作者	Ma, Dengke K.
作者单位	1.Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA 2.Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA 3.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Vozdek, Roman,Long, Yong,Ma, Dengke K.. The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury[J]. SCIENCE SIGNALING,2018,11(550):12.
APA	Vozdek, Roman,Long, Yong,&Ma, Dengke K..(2018).The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury.SCIENCE SIGNALING,11(550),12.
MLA	Vozdek, Roman,et al."The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury".SCIENCE SIGNALING 11.550(2018):12.

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