EGF-mediated migration signaling activated by N-acetylglucosaminyltransferase-V via receptor protein tyrosine phosphatase kappa.
N-acetylglucosaminyltransferase-V (GnT-V) has been reported to be closely associated with tumor migration, but the mechanism has been not currently clear. In this study we found that GnT-V activated EGFR signaling and promoted cell migration through receptor protein tyrosine phosphatase kappa (RPTPkappa). The overexpression of GnT-V gene in human hepatoma SMMC-7721 cell line not only induced the addition of beta1,6 GlcNAc branch to N-glycan of RPTPkappa but also decreased the protein level of RPTPkappa, which both contributed to the decreased phosphatase activity of RPTPkappa activating subsequently EGFR signaling. Moreover, we found that the knockdown of RPTPkappa and its addition of beta1,6 GlcNAc branch both promoted cell migration, which could be ascribed to the activation of EGFR signaling regulated by RPTPkappa. Therefore, our findings could provide an insight into the molecular mechanism of how GnT-V promoted cell migration, suggesting that RPTPkappa could be one of factors regulating the EGF-mediated migration signals.
Wang
Can
C
The Key Laboratory of Glycoconjugate Research, The Ministry of Health, Shanghai 200032, China.
Yang
Yong
Y
Yang
Zhaohua
Z
Liu
Mingzhu
M
Li
Zengxia
Z
Sun
Lidong
L
Mei
Chuanzhong
C
Chen
Hong
H
Chen
Liang
L
Wang
Liying
L
Zha
Xiliang
X
D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D066246:ErbB Receptors; C489852:PTPRK protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2