A novel protein tyrosine kinase NOK that shares homology with platelet- derived growth factor/fibroblast growth factor receptors induces tumorigenesis and metastasis in nude mice.
Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3'-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.
Liu
Li
L
Tsinghua Institute of Genome Research, Department of Biological Sciences and Biotechnology and Institute of Biomedicine, Tsinghua University, China. liu_li@mail.tsinghua.edu.cn
Yu
Xin-Zi
XZ
Li
Tie-Shi
TS
Song
Lian-Xia
LX
Chen
Pei-La
PL
Suo
Ta-Lin
TL
Li
Ying-Hua
YH
Wang
Shi-Dong
SD
Chen
Yue
Y
Ren
Yong-Ming
YM
Zhang
Shu-Ping
SP
Chang
Zhi-Jie
ZJ
Fu
Xin-Yuan
XY
D000818:Animals; D006801:Humans; D051379:Mice; D000595:Amino Acid Sequence; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D019556:COS Cells; D020935:MAP Kinase Signaling System / Q000235:genetics; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D015513:Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017468:Receptors, Fibroblast Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D012333:RNA, Messenger; C482299:STYK1 protein, human; C000731233:Styk1 protein, mouse