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- 학술저널
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- 2014.1
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The C-terminal fragment of the c-Met receptor tyrosine kinase is present in the nuclei of some cells irrespective of ligand stimulation, but the responsible nuclear localization signal (NLS) has not been previously reported. Here, we report that two histidine residues separated by a 10-amino-acid spacer (H1068–H1079) located in the juxtamembrane region of c-Met function as a putative novel NLS. Deletion of these sequences significantly abolished the nuclear translocation of c-Met, as did substitution of the histidines with alanines. This substitution also decreased the association of c-Met fragment with importin β. The putative NLS of c-Met is unique in that it relies on histidines, whose positive charge changes depending on pH, rather than the lysines or arginines, commonly found in classical bipartite NLSs, suggesting the possible ‘pH-dependency’ of this NLS. Indeed, decreasing the cytosolic pH either with nigericin, an Na+/H+ exchanger or pH 6.5 KRB buffer significantly increased the level of nuclear c-Met and the interaction of the c-Met fragment with importin β, indicating that low pH itself enhanced nuclear translocation. Consistent with this, nigericin treatment also increased the nuclear level of endogenous c-Met in HeLa cells. The putative aberrant bipartite NLS of c-Met seems to be the first example of what we call a ‘pH-dependent’ NLS.
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참고문헌 (24)
참고문헌 신청
Bae SS / 2001 / Proteolytic cleavage of epidermal growth factor receptor by caspases / FEBS Lett 491 : 16 ~ 20
Bandyopadhyay D / 1998 / Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells / J. Biol. Chem 273 : 1568 ~ 1573
Brown MS / 2000 / Regulated intramembrane proteolysis : a control mechanism conserved from bacteria to humans / Cell 100 : 391 ~ 398
Dittmann K / 2010 / Nuclear EGFR as novel therapeutic target: insights into nuclear translocation and function / Strahlentherapie und Onkologie: Organ der Deutschen Rontgeng
Hoppe T / 2000 / Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing / Cell 102 : 577 ~ 586
Bandyopadhyay D / 1998 / Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells / J. Biol. Chem 273 : 1568 ~ 1573
Brown MS / 2000 / Regulated intramembrane proteolysis : a control mechanism conserved from bacteria to humans / Cell 100 : 391 ~ 398
Dittmann K / 2010 / Nuclear EGFR as novel therapeutic target: insights into nuclear translocation and function / Strahlentherapie und Onkologie: Organ der Deutschen Rontgeng
Hoppe T / 2000 / Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing / Cell 102 : 577 ~ 586
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