The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling

Elina Mattila, Kaisa Auvinen, Marko Salmi, Johanna Ivaska (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Vascular endothelial growth factor (VEGF) is a major angiogenic factor that triggers formation of new vessels under physiological and pathological conditions. However, the mechanisms that limit the VEGF responses in target cells and hence prevent excessive and harmful angiogenesis are not well understood. Here, our objective was to study whether T-cell protein tyrosine phosphatase (TCPTP, also known as PTN2), which we found to be expressed in human endothelial cells, could alter VEGF signalling by controlling phosphorylation of VEGFR2. We show that a TCPTP substrate-trapping mutant interacts with VEGFR2. Moreover, TCPTP dephosphorylates VEGFR2 in a phosphosite-specific manner, inhibits its kinase activity and prevents its internalization from the cell surface. We found that TCPTP activity is induced upon integrin-mediated binding of endothelial cells to collagen matrix. TCPTP activation was also induced by using cell-permeable peptides from the cytoplasmic tail of the collagen-binding integrin α1. Controlled activation of TCPTP results in inhibition of VEGF-triggered endothelial cell proliferation, angiogenic sprouting, chemokinesis and chemotaxis. We conclude that matrix-controlled TCPTP phosphatase activity can inhibit VEGFR2 signalling, and the growth, migration and differentiation of human endothelial cells.
Original languageEnglish
Pages (from-to)3570-3580
JournalJournal of Cell Science
Volume121
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

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Protein Tyrosine Phosphatases
Vascular Endothelial Growth Factor A
Endothelial Cells
Integrins
Non-Receptor Type 2 Protein Tyrosine Phosphatase
Collagen
Angiogenesis Inducing Agents
Chemotaxis
Phosphoric Monoester Hydrolases
Tail
Phosphotransferases
Phosphorylation
Cell Proliferation
Peptides
Growth

Cite this

Mattila, Elina ; Auvinen, Kaisa ; Salmi, Marko ; Ivaska, Johanna. / The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling. In: Journal of Cell Science. 2008 ; Vol. 121. pp. 3570-3580.
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title = "The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling",
abstract = "Vascular endothelial growth factor (VEGF) is a major angiogenic factor that triggers formation of new vessels under physiological and pathological conditions. However, the mechanisms that limit the VEGF responses in target cells and hence prevent excessive and harmful angiogenesis are not well understood. Here, our objective was to study whether T-cell protein tyrosine phosphatase (TCPTP, also known as PTN2), which we found to be expressed in human endothelial cells, could alter VEGF signalling by controlling phosphorylation of VEGFR2. We show that a TCPTP substrate-trapping mutant interacts with VEGFR2. Moreover, TCPTP dephosphorylates VEGFR2 in a phosphosite-specific manner, inhibits its kinase activity and prevents its internalization from the cell surface. We found that TCPTP activity is induced upon integrin-mediated binding of endothelial cells to collagen matrix. TCPTP activation was also induced by using cell-permeable peptides from the cytoplasmic tail of the collagen-binding integrin α1. Controlled activation of TCPTP results in inhibition of VEGF-triggered endothelial cell proliferation, angiogenic sprouting, chemokinesis and chemotaxis. We conclude that matrix-controlled TCPTP phosphatase activity can inhibit VEGFR2 signalling, and the growth, migration and differentiation of human endothelial cells.",
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Mattila, E, Auvinen, K, Salmi, M & Ivaska, J 2008, 'The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling', Journal of Cell Science, vol. 121, pp. 3570-3580. https://doi.org/10.1242/jcs.031898

The protein tyrosine phosphatase TCPTP controls VEGFR2 signalling. / Mattila, Elina; Auvinen, Kaisa; Salmi, Marko; Ivaska, Johanna (Corresponding Author).

In: Journal of Cell Science, Vol. 121, 2008, p. 3570-3580.

Research output: Contribution to journalArticleScientificpeer-review

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AB - Vascular endothelial growth factor (VEGF) is a major angiogenic factor that triggers formation of new vessels under physiological and pathological conditions. However, the mechanisms that limit the VEGF responses in target cells and hence prevent excessive and harmful angiogenesis are not well understood. Here, our objective was to study whether T-cell protein tyrosine phosphatase (TCPTP, also known as PTN2), which we found to be expressed in human endothelial cells, could alter VEGF signalling by controlling phosphorylation of VEGFR2. We show that a TCPTP substrate-trapping mutant interacts with VEGFR2. Moreover, TCPTP dephosphorylates VEGFR2 in a phosphosite-specific manner, inhibits its kinase activity and prevents its internalization from the cell surface. We found that TCPTP activity is induced upon integrin-mediated binding of endothelial cells to collagen matrix. TCPTP activation was also induced by using cell-permeable peptides from the cytoplasmic tail of the collagen-binding integrin α1. Controlled activation of TCPTP results in inhibition of VEGF-triggered endothelial cell proliferation, angiogenic sprouting, chemokinesis and chemotaxis. We conclude that matrix-controlled TCPTP phosphatase activity can inhibit VEGFR2 signalling, and the growth, migration and differentiation of human endothelial cells.

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