Mechanism of Dimerization of a Recombinant Mature Vascular Endothelial Growth Factor C

被引：16

作者：

Chiu, Joyce ^{[1
,2
]}

Wong, Jason W. H. ^{[1
,2
]}

Gerometta, Michael ^{[3
]}

Hogg, Philip J. ^{[1
,2
]}

机构：

[1] Univ New S Wales, Lowy Canc Res Ctr, Sydney, NSW 2052, Australia

[2] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW 2052, Australia

[3] Vegenics Pty Ltd, Circadian Technol Ltd, Yarra, Vic 3141, Australia

来源：

BIOCHEMISTRY | 2014年 / 53卷 / 01期

基金：

英国医学研究理事会;

关键词：

LYMPHATIC VESSELS; VEGF-C; METASTASIS;

D O I：

10.1021/bi401518b

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The vascular endothelial growth factors (VEGFs) and their tyrosine kinase receptors play a pivotal role in angiogenesis and lymphangiogenesis during development and in pathologies such as tumor growth. The VEGFs function as disulfide-linked antiparallel homodimers. The lymphangiogenic factors, VEGF-C and VEGF-D, exist as monomers and dimers, and dimerization is regulated by a unique unpaired cysteine. In this study, we have characterized the redox state of this unpaired cysteine in a recombinant mature monomeric and dimeric VEGF-C by mass spectrometry. Our findings indicate that the unpaired cysteine regulates dimerization via thiol-disulfide exchange involving the interdimer disulfide bond.

引用

页码：7 / 9

页数：3

共 16 条

[1] Molecular control of lymphatic metastasis [J].

Achen, Marc G. ;

Stacker, Steven A. .

LYMPHATIC CONTINUUM REVISITED, 2008, 1131 :225-234

[2] Activated Forms of VEGF-C and VEGF-D Provide Improved Vascular Function in Skeletal Muscle [J].

Anisimov, Andrey ;

Alitalo, Annamari ;

Korpisalo, Petra ;

Soronen, Jarkko ;

Kaijalainen, Seppo ;

Leppanen, Veli-Matti ;

Jeltsch, Michael ;

Yla-Herttuala, Seppo ;

Alitalo, Kari .

CIRCULATION RESEARCH, 2009, 104 (11) :1302-U156

[3] Vascular endothelial growth factor d is dispensable for development of the lymphatic system [J].

Baldwin, ME ;

Halford, MA ;

Roufail, S ;

Williams, RA ;

Hibbs, ML ;

Grail, D ;

Kubo, H ;

Stacker, SA ;

Achen, MG .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (06) :2441-2449

[4] Preparation of human vascular endothelial growth factor-D for structural and preclinical therapeutic studies [J].

Davydova, Natalia ;

Streltsov, Victor A. ;

Roufail, Sally ;

Lovrecz, George O. ;

Stacker, Steven A. ;

Adams, Timothy E. ;

Achen, Marc G. .

PROTEIN EXPRESSION AND PURIFICATION, 2012, 82 (01) :232-239

[5] Lateral self-association of VWF involves the Cys2431-Cys2453 disulfide/dithiol in the C2 domain [J].

Ganderton, Tim ;

Wong, Jason W. H. ;

Schroeder, Christina ;

Hogg, Philip J. .

BLOOD, 2011, 118 (19) :5312-5318

[6] Vascular endothelial cell growth factor receptor 3-mediated activation of lymphatic endothelium is crucial for tumor cell entry and spread via lymphatic vessels [J].

He, YL ;

Rajantie, I ;

Pajusola, K ;

Jeltsch, M ;

Holopainen, T ;

Yla-Herttuala, S ;

Harding, T ;

Jooss, K ;

Takahashi, T ;

Alitalo, K .

CANCER RESEARCH, 2005, 65 (11) :4739-4746

[7] Targeting allosteric disulphide bonds in cancer [J].

Hogg, Philip J. .

NATURE REVIEWS CANCER, 2013, 13 (06) :425-431

[8]

Joukov V, 1996, EMBO J, V15, P290

[9] Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins [J].

Karkkainen, MJ ;

Haiko, P ;

Sainio, K ;

Partanen, J ;

Taipale, J ;

Petrova, TV ;

Jeltsch, M ;

Jackson, DG ;

Talikka, M ;

Rauvala, H ;

Betsholtz, C ;

Alitalo, K .

NATURE IMMUNOLOGY, 2004, 5 (01) :74-80

[10] Structural determinants of vascular endothelial growth factor-D receptor binding and specificity [J].

Leppanen, Veli-Matti ;

Jeltsch, Michael ;

Anisimov, Andrey ;

Tvorogov, Denis ;

Aho, Kukka ;

Kalkkinen, Nisse ;

Toivanen, Pyry ;

Yla-Herttuala, Seppo ;

Ballmer-Hofer, Kurt ;

Alitalo, Kari .

BLOOD, 2011, 117 (05) :1507-1515

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