title: The carboxyl terminal tyrosine 417 residue of NOK has an autoinhibitory effect on NOK-mediated signaling transductions.
abstract: Receptor protein tyrosine kinases (RPTKs) are essential mediators of cell growth, differentiation, migration, and metabolism. Recently, a novel RPTK named NOK has been cloned and characterized. In current study, we investigated the role of the carboxyl terminal tyrosine 417 residue of NOK in the activations of different signaling pathways. A single tyrosine to phenylalanine point mutation at Y417 site (Y417F) not only dramatically enhanced the NOK-induced activation of extracellular signal-regulated kinase (ERK), but also markedly promoted the NOK-mediated activation of both signal transducer and activator of transcription 1 and 3 (STAT1 and 3). Moreover, the proliferation potential of NIH3T3-NOK (Y417F) stable cells were significantly elevated as compared with that of NIH3T3-NOK. Overall, our results demonstrate that the tyrosine Y417 residue at the carboxyl tail of NOK exhibits an autoinhibitory role in NOK-mediated signaling transductions.
authors: Tsinghua Institute of Genome Research, Institute of Biomedicine & School of Medicine, Tsinghua University, Beijing 100084, China.
authors: Ying-Hua
authors: YH
authors: Li
authors: Shan
authors: S
authors: Zhong
authors: Zhi-Li
authors: ZL
authors: Rong
authors: Yong-Ming
authors: YM
authors: Ren
authors: Zhi-Yong
authors: ZY
authors: Li
authors: Shu-Ping
authors: SP
authors: Zhang
authors: Zhijie
authors: Z
authors: Chang
authors: Li
authors: L
authors: Liu
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D019943:Amino Acid Substitution; D049109:Cell Proliferation; D002478:Cells, Cultured; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors; D014443:Tyrosine / Q000502:physiology
chemical_list: D020928:Mitogen-Activated Protein Kinases; D015513:Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D050791:STAT Transcription Factors; D014443:Tyrosine; C000731233:Styk1 protein, mouse