Identification of novel nuclear localization signal within the ErbB-2 protein.
ErbB2, a member of the receptor tyrosine kinase family, is frequently over-expressed in breast cancer. Proteolysis of the extracellular domain of ErbB2 results in constitutive activation of ErbB2 kinase. Recent study reported that ErbB2 is found in the nucleus. Here, we showed that ErbB2 is imported into the nucleus through a nuclear localization signal (NLS)-mediated mechanism. The NLS sequence KRRQQKIRKYTMRR (aa655-668) contains three clusters of basic amino acids and it is sufficient to target GFP into the nucleus. However, mutation in any basic amino acid cluster of this NLS sequence significantly affects its nuclear localization. Furthermore, it was found that this NLS is essential for the nuclear localization of ErbB2 since the intracellular domain of Erb2 lacking NLS completely abrogates its nuclear translocation. Taken together, our study identified a novel nuclear localization signal and reveals a novel mechanism underlying ErbB2 nuclear trafficking and localization.
Chen
Qiao Qiao
QQ
School of Life Science, University of Science and Technology of China, Hefei 230027, China.
Chen
Xiao Ying
XY
Jiang
Yun Yun
YY
Liu
Jing
J
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019913:Nuclear Localization Signals / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; D018076:DNA, Complementary; D019913:Nuclear Localization Signals; D018719:Erb-b2 Receptor Tyrosine Kinases