Protein phosphorylation on tyrosine residues is an important cell signaling mechanism that is regulated by the antagonistic activities of the protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). We are interested in the function of PTPs in development and cell signaling. Using biochemical and cell biological approaches, we found that the proto-typical RPTPalpha is regulated by dimerization, oxidation and phosphorylation. The zebrafish is used to elucidate the role of PTPs and PTKs in early vertebrate development. Recently, we found that several PTKs and PTPs are essential for normal convergence and extension cell movements in gastrulation.
About the research
Choorapoikayil S, Kers R, Herbomel P, Kissa K and den Hertog J (2014) Pivotal role of Pten in the balance between proliferation and differentiation of hematopoietic stem cells in zebrafish. Blood 123, 184-190
Bonetti M, Paardekooper Overman J, Tessadori F, Noël E, Bakkers J and den Hertog J (2014) Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish. Development 141, 1961-1970
Jopling, C., van Geemen, D., den Hertog, J. (2007) Shp2 knock down and Noonan/LEOPARD mutant Shp2 induced gastrulation cell movement defects in zebrafish. PLoS Genet. 3: e225.
Blanchetot, C., Tertoolen, L.G.J., den Hertog, J. (2002) Regulation of receptor protein tyrosine phosphatase alpha by oxidative stress. EMBO J. 21: 493-503.
den Hertog, J., Pals, C.E.G.M., Peppelenbosch, M.P., Tertoolen, L.G.J., de Laat, S.W., Kruijer, W. (1993) Receptor protein-tyrosine phosphatase alpha activates pp60c-src and is involved in neuronal differentiation. EMBO J. 12: 3789-3798.
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