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Angiogenesis
Published in: Angiogenesis 1/2009

01-03-2009 | Original Paper

Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells

Authors: Orisha K. Yacyshyn, Patrick F. H. Lai, Kelly Forse, Krystyna Teichert-Kuliszewska, Paul Jurasz, Duncan J. Stewart

Published in: Angiogenesis | Issue 1/2009

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Abstract

Objectives

The endothelial cell (EC)-selective receptor tyrosine kinase, Tie2, and its ligands angiopoietin Ang-1 and Ang-2, are essential for blood vessel maintenance and repair. Ang-1 is an agonist of Tie2 receptor activation, whereas Ang-2 is a context-dependent antagonist/agonist. Therefore, we investigated the role of the EC-selective phosphatase, human protein tyrosine phosphatase beta (HPTPβ), in regulating Tie2 activity.

Methods and results

siRNA silencing of HPTPβ enhanced Ang-1 and Ang-2-induced Tie2 phosphorylation at 10 min (2.5-fold, P < 0.001; and 1.8-fold, P < 0.05, respectively). The cell survival response to Ang-1, but not Ang-2, was enhanced by HPTPβ silencing as measured by flow cytometry (0.85-fold to 0.66-fold, P < 0.05) and ELISA (0.88-fold to 0.53-fold, P < 0.01). Hypoxia, which upregulated HPTPβ expression in endothelial cells, impaired Ang-1-induced Tie2 phosphorylation.

Conclusions

These results reveal a novel role for HPTPβ in modulating Ang-1-Tie2 signaling and endothelial cell survival.
Literature
1.
Dumont DJ, Gradwohl G, Fong GH, Puri MC, Gertsenstein M, Auerbach A, Breitman ML (1994) Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. Genes Dev 8:1897–1909. doi:10.​1101/​gad.​8.​16.​1897 PubMedCrossRef
2.
Kim I, Kim HG, So JN, Kim JH, Kwak HJ, Koh GY (2000) Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Circ Res 86:24–29PubMed
3.
Jones N, Voskas D, Master Z, Sarao R, Jones J, Dumont DJ (2001) Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function. EMBO Rep 2:438–445PubMed
4.
5.
Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60. doi:10.​1126/​science.​277.​5322.​55 PubMedCrossRef
6.
Teichert-Kuliszewska K, Maisonpierre PC, Jones N, Campbell AI, Master Z, Bendeck MP, Alitalo K, Dumont DJ, Yancopoulos GD, Stewart DJ (2001) Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2. Cardiovasc Res 49:659–670. doi:10.​1016/​S0008-6363(00)00231-5 PubMedCrossRef
7.
8.
Kim I, Kim JH, Moon SO, Kwak HJ, Kim NG, Koh GY (2000) Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway. Oncogene 19:4549–4552. doi:10.​1038/​sj.​onc.​1203800 PubMedCrossRef
9.
10.
11.
Witzenbichler B, Maisonpierre PC, Jones P, Yancopoulos GD, Isner JM (1998) Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. J Biol Chem 273:18514–18521. doi:10.​1074/​jbc.​273.​29.​18514 PubMedCrossRef
12.
Baumer S, Keller L, Holtmann A, Funke R, August B, Gamp A, Wolburg H, Wolburg-Buchholz K, Deutsch U, Vestweber D (2006) Vascular endothelial cell-specific phosphotyrosine phosphatase (VE–PTP) activity is required for blood vessel development. Blood 107:4754–4762. doi:10.​1182/​blood-2006-01-0141 PubMedCrossRef
13.
14.
Dominguez MG, Hughes VC, Pan L, Simmons M, Daly C, Anderson K, Noguera-Troise I, Murphy AJ, Valenzuela DM, Davis S, Thurston G, Yancopoulos GD, Gale NW (2007) Vascular endothelial tyrosine phosphatase (VE–PTP)-null mice undergo vasculogenesis but die embryonically because of defects in angiogenesis. Proc Natl Acad Sci USA 104:3243–3248. doi:10.​1073/​pnas.​0611510104 PubMedCrossRef
15.
16.
Huang L, Turck CW, Rao P, Peters KG (1995) GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK/TIE2 receptor tyrosine kinase. Oncogene 11:2097–2103PubMed
17.
Huang L, Sankar S, Lin C, Kontos CD, Schroff AD, Cha EH, Feng SM, Li SF, Yu Z, Van Etten RL, Blanar MA, Peters KG (1999) HCPTPA, a protein tyrosine phosphatase that regulates vascular endothelial growth factor receptor-mediated signal transduction and biological activity. J Biol Chem 274:38183–38188. doi:10.​1074/​jbc.​274.​53.​38183 PubMedCrossRef
18.
Krueger NX, Streuli M, Saito H (1990) Structural diversity and evolution of human receptor-like protein tyrosine phosphatases. EMBO J 9:3241–3252PubMed
19.
Harder KW, Anderson LL, Duncan AM, Jirik FR (1992) The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15-q21. Cytogenet Cell Genet 61:269–270. doi:10.​1159/​000133419 PubMedCrossRef
20.
21.
Gaits F, Li RY, Ragab A, Ragab-Thomas JM, Chap H (1995) Increase in receptor-like protein tyrosine phosphatase activity and expression level on density-dependent growth arrest of endothelial cells. Biochem J 311(Pt 1):97–103PubMed
22.
Gaits F, Li RY, Ragab A, Selves J, Ragab-Thomas JM, Chap H (1994) Implication of a protein-tyrosine-phosphatase in human lung cancer. Cell Mol Biol (Noisy -le-grand) 40:677–685
23.
Kim I, Kim HG, Moon SO, Chae SW, So JN, Koh KN, Ahn BC, Koh GY (2000) Angiopoietin-1 induces endothelial cell sprouting through the activation of focal adhesion kinase and plasmin secretion. Circ Res 86(9):952–959PubMed
24.
Harfouche R, Gratton JP, Yancopoulos GD, Noseda M, Karsan A, Hussain SN (2003) Angiopoietin-1 activates both anti- and proapoptotic mitogen-activated protein kinases. FASEB J 17:1523–1525PubMed
25.
26.
27.
Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, Vestweber D (2002) VE–PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. EMBO J 21(18):4885–4895. doi:10.​1093/​emboj/​cdf497 PubMedCrossRef
Metadata
Title
Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells
Authors
Orisha K. Yacyshyn
Patrick F. H. Lai
Kelly Forse
Krystyna Teichert-Kuliszewska
Paul Jurasz
Duncan J. Stewart
Publication date
01-03-2009
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 1/2009
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-008-9126-0

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