The carboxyl terminal tyrosine 417 residue of NOK has an autoinhibitory effect on NOK-mediated signaling transductions.
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.
Li
Ying-Hua
YH
Tsinghua Institute of Genome Research, Institute of Biomedicine & School of Medicine, Tsinghua University, Beijing 100084, China.
Zhong
Shan
S
Rong
Zhi-Li
ZL
Ren
Yong-Ming
YM
Li
Zhi-Yong
ZY
Zhang
Shu-Ping
SP
Chang
Zhijie
Z
Liu
Li
L
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
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