Jeroen den Hertog

Jeroen den Hertog studied chemistry at Utrecht University (1983-1988). He received his PhD from Utrecht University in 1992, based on work done at the Hubrecht Institute, supervised by Wiebe Kruijer and Siegfried de Laat. He was awarded a fellowship from the Dutch Cancer Society (Koningin Wilhelmina Fonds) and did a postdoctoral with Tony Hunter at the Salk Institute, La Jolla, CA, USA from 1992-1994. In 1994 he became project leader at the Hubrecht Institute and in 1997 group leader. While maintaining his position as a group leader, he was appointed deputy director research at the Hubrecht Institute and professor of Molecular Developmental Zoology at the University of Leiden in 2008. He has received several grants from the Dutch Cancer Society (Koningin Wilhelmina Fonds), Netherlands Organization for Scientific Research (NWO/ALW) and Netherlands Proteomics Centre (NPC). He was involved in a European Research Training Network (FP5) and in a Marie Curie Research Training Network.

Other activitites:

  • Professor at Leiden University

j.denhertog(at)hubrecht.eu

Team members den Hertog

Ali Kiai

MSc student

Ali Kiai

Sasja Blokzijl-Franke

PhD student

Sasja Blokzijl-Franke

Petra A. Bakker

PhD student

Petra A. Bakker

Alexander James Hale

PhD Student

Walbert Bakker

Guest

Walbert Bakker

Jelmer Hoeksma

Technician

Loes van Dam

Guest

Loes van Dam

Miriam Stumpf

Guest

Miriam Stumpf

Anna Blokhuis

Guest

Anna Blokhuis

Khalid al Makrini

student

Khalid al Makrini

John Overvoorde

Lab Assistant

Michiel van Gent

Guest

Michiel van Gent

Jeroen den Hertog

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Research

Den Hertog: Protein-tyrosine phosphatases in development

Protein phosphorylation on tyrosine residues is an important cell signaling mechanism that is crucial for cell proliferation, migration and transformation. Tyrosine phosphorylation 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. We use zebrafish as a model to elucidate the role of PTPs and PTKs in early vertebrate development. Recently, we found that several PTKs and PTPs are essential for normal...

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Key publications

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.

All publications

2016

Stumpf M, Blokzijl-Franke S, den Hertog J (2016) Fine-tuning of Pten localization and phosphatase activity is essential for zebrafish angiogenesis PLoS One 11, e0154771

Blokhuis AM, Koppers M, Groen EJN, Dini Modigliani S, van den Heuvel DMA, Anink JJ, Fumoto K, van Diggelen F, Snelting A, Sodaar P, Demmers JAA, Veldink JH, Aronica E, Bozzoni I, den Hertog J, van den Berg LH, Pasterkamp RJ (2016) Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways. Acta Neurpath, in press

Stumpf M, den Hertog J (2016) Differential Requirement for Pten Lipid and Protein Phosphatase Activity during Zebrafish Embryonic Development. PLoS One 11, e0148508

Stanford SM, Svensson MN, Sacchetti C, Pilo CA, Wu DJ, Kiosses WB, Hellvard A, Bergum B, Aleman Muench GR, Elly C, Liu YC, den Hertog J, Elson A, Sap J, Mydel P, Boyle DL, Corr M, Firestein GS, Bottini N. (2015) Receptor protein tyrosine phosphatase alpha enhances rheumatoid synovial fibroblast signaling and promotes arthritis in mice. Arthritis Rheumatol 68, 359-369

2015

Stumpf M, Choorapoikayil S and den Hertog J (2015) Pten function in zebrafish: Anything but a fish story. Methods, 77-78, 191-196

Vissers LELM, Bonetti M, Paardekooper Overman J, Nillesen WM, Frints SGM, de Ligt J, Zampino G, Justino A, Machado JC, Schepens M, Brunner HG, Veltman JA, Scheffer H, Gros P, Costa JL, Tartaglia M, van der Burgt I, Yntema HG and den Hertog J (2015) Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome. Eur J Hum Gen, 23, 317-324

2014

Paardekooper Overman J, Preisinger C, Prummel K, Bonetti M, Giansanti P, Heck A and den Hertog J (2014) Phosphoproteomics-mediated identification of Fer kinase as a target of mutant Shp2 in Noonan and LEOPARD syndrome. PLoS ONE 9, e106682

Pulido R, Baker SJ, Barata JT, Carracedo A, Cid VJ, Chin-Sang ID, Davé V, den Hertog J, Devreotes P, Eickholt BJ, Eng C, Furnari FB, Georgescu MM, Gericke A, Hopkins B, Jiang X, Lee SR, Lösche M, Malaney P, Matias-Guiu X, Molina M, Pandolfi PP, Parsons R, Pinton P, Rivas C, Rocha RM, Rodríguez MS, Ross AH, Serrano M, Stambolic V, Stiles B, Suzuki A, Tan SS, Tonks NK, Trotman LC, Wolff N, Woscholski R, Wu H, Leslie NR (2014) A Unified Nomenclature and Amino Acid Numbering for Human PTEN. Sci Signal 7, pe15.

Paardekooper Overman J, Yi JS, Bonetti M, Soulsby M, Preisinger C, Stokes MP, Hui L, Silva JC, Overvoorde J, Giansanti P, Heck AJR, Kontaridis MI, den Hertog J and Bennett AM (2014) PZR coordinates Noonan and LEOPARD syndrome signaling in zebrafish and mice. Mol Cell Biol 34, 2874–2889

Leslie NR and den Hertog J (2014) Mutant PTEN in cancer: worse than nothing. Cell 157, 527-529

Finkelshtein E, Lotinun S, Levy-Apter E, Arman E, den Hertog J, Baron R and Elson A (2014) Protein tyrosine phosphatases Epsilon and Alpha perform non-redundant roles in osteoclasts. Mol Biol Cell, 25, 1808-1818

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

Bonetti M, Rodriguez-Martinez V, Paardekooper Overman J, Overvoorde J, van Eekelen M, Jopling C and den Hertog J (2014) Distinct and overlapping functions of ptpn11 genes in zebrafish development. PLoS ONE, 9, e94884.

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

Albers HMHG, Kuijl C, Bakker J, Hendrickx L, Wekker S, Farhou N, Liu N, Blasco-Moreno B, Scanu T, den Hertog J, Celie P, Ovaa H and Neefjes J (2014) Integrating chemical and genetic silencing strategies to identify host kinase-phosphatase inhibitor networks that control bacterial infection. ACS Chem Biol 9, 414-422

van Ameijde J, Overvoorde J, Knapp S, den Hertog J, Ruijtenbeek R, Liskamp RM (2014) A versatile spectrophotometric protein tyrosine phosphatase assay based on 3-nitrophosphotyrosine containing substrates. Anal Biochem. 448C, 9-13

Paardekooper Overman J and den Hertog J (2014) Zebrafish as a model to study PTPs during development. Methods 65, 247-253

2013

Noël ES, Verhoeven M, Lagendijk AK, Tessadori F, Smith K, Choorapoikayil S, den Hertog J, Bakkers J (2013) A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality. Nat Commun 4, 2754

Choorapoikayil S, Weijts B, Kers R, de Bruin A, den Hertog J (2013) Loss of Pten promotes angiogenesis and enhanced vegfaa expression in zebrafish. Dis Mod Mech, 6, 1159-1166

Choorapoikayil S, Overvoorde J, den Hertog J (2013) Deriving Cell Lines from Zebrafish Embryos and Tumors. Zebrafish, 10, 316-325

Hendriks WJ, Elson A, Harroch S, Pulido R, Stoker A, den Hertog J (2013) Protein tyrosine phosphatases in health and disease. FEBS J, 280, 708–730

Böhmer F, Szedlacsek S, Tabernero L, Ostman A, den Hertog J (2012) Protein tyrosine phosphatase structure-function relationships in regulation and pathogenesis. FEBS J., 280, 413–431

Kanwal Z, Zakrzewska A, den Hertog J, Spaink HP, Schaaf MJM, Meijer AH (2013) Deficiency in hematopoietic phosphatase Ptpn6/Shp1 hyperactivates the innate immune system and impairs control of bacterial infections in zebrafish embryos. J. Immunol., 190, 1631-1645

Guida V, Ferese R, Rocchetti M, Bonetti M, Sarkozy A, Cecchetti S, Gelmetti V, Lepri F, Copetti M, Lamorte G, Digilio MC, Marino B, Zaza A, den Hertog J, Dallapiccola B, De Luca A (2013) A variant in the carboxyl-terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot. Eur J Hum Gen 21, 69-75

2012

Ferreira PA, Ruela-de-Sousa RR, Queiroz KC, Souza AC, Milani R, Pilli RA, Peppelenbosch MP, den Hertog J, Ferreira CV (2012) Knocking Down Low Molecular Weight Protein Tyrosine Phosphatase (LMW-PTP) Reverts Chemoresistance through Inactivation of Src and Bcr-Abl Proteins. PLoS ONE 7, e44312

van Eekelen M, Runtuwene V, Masselink W, den Hertog J (2012) Pair-Wise Regulation of Convergence and Extension Cell Movements by Four Phosphatases via RhoA. PLoS ONE 7, e35913

Choorapoikayil S, Kuiper RV, de Bruin A, den Hertog J (2012) Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma. Dis Mod Mech, 5, 241-247

2011

Gutierrez A, Grebliunaite R, Feng H, Kozakewich E, Zhu S, Guo F, Payne E, Mansour M, Dahlberg SE, Neuberg DS, den Hertog J, Prochownik EV, Testa JR, Harris M, Kanki JP, Look AT (2011) Pten Mediates Myc Oncogene Dependence in a Conditional Zebrafish Model of T-ALL. J Exp Med, 208, 1595-1603

Runtuwene V, van Eekelen M, Overvoorde J, Rehmann H, Yntema HG, Nillesen WM, van Haeringen A, van der Burgt I, Burgering B, den Hertog J (2011) Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects. Dis Mod Mech 4, 393-399

2010

van Eekelen M, Overvoorde J, van Rooijen C and den Hertog J. (2010) Identification and expression of the family of classical protein-tyrosine phosphatases in zebrafish. PLoS ONE 5, e12573

Vacaru AM, den Hertog J. (2010) Serine dephosphorylation of RPTP{alpha} in mitosis induced Src binding and activation. Mol Cell Biol. 30, 2850-2861

van Eekelen M, Runtuwene V, Overvoorde J, den Hertog J. (2010) RPTPalpha and PTPepsilon signaling via Fyn/Yes and RhoA is essential for zebrafish convergence and extension cell movements during gastrulation. Dev Biol. 340, 626-639

Vacaru, A.M. and den Hertog, J. (2010) Catalytically active membrane-distal phosphatase domain of RPTPα is required for Src activation. FEBS J. 277, 1562–1570

Boersema PJ, Foong LY, Ding VM, Lemeer S, van Breukelen B, Philp R, Boekhorst J, Snel B, den Hertog J, Choo AB, Heck AJ. (2010) In depth qualitative and quantitative profiling of tyrosine phosphorylation using a combination of phosphopeptide immuno-affinity purification and stable isotope dimethyl labeling. Mol Cell Prot. 9, 84-99

2009

Vacaru, A.M. and den Hertog, J. (2009) Reciprocal regulation of RPTPalpha and Src. Rom. J. Biochem. 46, 187-197
den Hertog J, van Eekelen M (2009) Zebrafish and phosphatase function. Handbook of Cell Signaling, Bradshaw R, Dennis E (eds) Chapter 101.

2008

Rodriguez, F., Vacaru, A., Overvoorde, J. and den Hertog, J. (2008) The receptor protein-tyrosine phosphatase, Dep1, acts in arterial/venous cell fate decisions in zebrafish development. Dev. Biol. 324, 122-130

Lemeer, S., Jopling, C., Gouw, J., Mohammed, S., Heck, A.J.R., Slijper, M. and den Hertog, J. (2008) Comparative phosphoproteomics of zebrafish Fyn/Yes morpholino knockdown embryos. Mol. Cell. Prot., 7, 2176-2187

Bodrikov, V., Sytnyk, V., Leshchyns’ka, I., den Hertog, J. and Schachner, M. (2008) NCAM induces CaMKIIalpha-mediated RPTPalpha phosphorylation to enhance its catalytic activity and enhance neurite outgrowth. J. Cell Biol., 182, 1185-1200.

Cid, V.J., Rodrıguez-Escudero, I., Andres-Pons, A., Roma-Mateo, C., Gil, A., den Hertog, J., Molina, M. and Pulido, R. (2008) Assessment of PTEN tumor suppressor activity in nonmammalian models: the year of the yeast. Oncogene, 27, 5431-5442

Groen, A., Overvoorde, J., van der Wijk, T. and den Hertog, J. (2008) Redox regulation of dimerization of the Receptor Protein-Tyrosine Phosphatases RPTPα, LAR, RPTPμ and CD45. FEBS J. 275, 2597–2604

Bispo de Jesus, M, Zambuzzi, W.F., Ruela de Sousa, R.R., Areche, C., Santos de Souza, A.C., Aoyama, H., Schmeda-Hirschmann, G., Rodríguez, J.A., Monteiro de Souza Brito, A.R., Peppelenbosch, M.P., den Hertog, J., de Paula, E., Ferreira, C.V. (2008) Ferruginol suppresses survival signaling pathways in androgen-independent human prostate cancer cells. Biochimie, 90, 843-854

Lemeer, S., Pinkse, M.W.H., Mohammed, S., van Breukelen, B., den Hertog, J. Slijper, M. and Heck, A.J.R. (2008) On-line automated zebrafish phosphoproteomics; From large-scale analysis down-to a single embryo. J. Prot. Res. 7, 1555-1564

den Hertog, J. Östman, A and Böhmer, F.-D. (2008) Regulation of protein-tyrosine phosphatases. FEBS J. 275, 831–847

Faucherre, A., Taylor, G.S., Overvoorde, J., Dixon, J.E. and den Hertog, J. (2008) Zebrafish pten genes have overlapping and non-redundant functions in tumorigenesis and embryonic development. Oncogene 27, 1079–1086

2007

Jopling, C., van Geemen, D. and den Hertog, J. (2007) Shp2 knock down and Noonan/LEOPARD mutant Shp2 induced gastrulation cell movement defects in zebrafish. PLoS Genetics 3, e225

Lemeer, S.M., Ruijtenbeek, R., Pinkse, M.W.H., Jopling, C., Heck, A.J.R., den Hertog, J. and Slijper, M. (2007) Endogenous phosphotyrosine signaling in zebrafish embryos. Mol. Cell. Prot. 6, 2088-2099

Lemeer, S., Jopling, C., Naji, F., Ruijtenbeek, R., Slijper, M., Heck, A.J.R. and den Hertog, J. (2007) Protein-tyrosine kinase activity profiling in knock down zebrafish embryos. PLoS One 2(7): e581.

Knöll, R., Postel, R., Wang, J., Krätzner, R., Hennecke, G., Vacaru, A.M., Vakeel, P., Schubert, C., Murthy, K., Rana, B.K., Kube, D., Knöll, G., Schäfer, K., Hayashi, T., Holm, T., Kimura, A. Schork, N., Toliat, M.R., Nürnberg, P., Schultheiss, H.P., Schaper, W., Schaper, J., Bos, E., Den Hertog, J., van Eeden, F.J.M., Peters, P.J., Hasenfuss, G., Chien, K.R.and Bakkers, J. (2007) Laminin alpha 4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and in endothelial cells. Circulation 116, 515-525.

Jopling, C. and den Hertog, J. (2007) Essential role for Csk upstream of Fyn and Yes in zebrafish gastrulation. Mech. of Dev. 124, 129-136

Yang, J., Groen, A., Lemeer, S., Jans, A., Slijper, M., Roe, S.M., den Hertog, J. and Barford, D. (2007) Reversible oxidation of the membrane distal domain of receptor PTPalpha is mediated by a cyclic sulphenamide. Biochemistry 46, 709-719

2006

Diks, S.H., Bink, R.J., van de Water, S., Joore, J., van Rooijen, C., Verbeek, F.J., den Hertog, J., Peppelenbosch, M.P., Zivkovic, D. (2006) The novel gene asb11: a regulator of the size of the neural progenitor compartment. J. Cell Biol. 174, 581-592

Mitola, S., Brenchio, B., Piccinini, M., Tertoolen, L., Zammataro, L., Breier, G., Rinaudo, M.T., den Hertog, J. and Bussolino, F. (2006) Type I collagen limits VEGFR-2 signaling by a SHP2 protein-tyrosine phosphatase – dependent mechanism. Circ. Res. 98, 45-54

2005

Hsia, D.A., Lim, S.T., Bernard-Triflo, J.A., Mitra, S.K., Tanaka, S., den Hertog, J., Streblow, D.N., Ilic, D., Ginsberg, M.H. and Schlaepfer, D.D. (2005) Integrin alpha4beta1 promotes FAK-independent cell motility via alpha4 cytoplasmic domain-specific activation of c-Src. Mol. Cell. Biol. 25, 9700 – 9712

De Guzman, B., Hisatsune, J., Nakayama, M., Yahiro, K., Wada, A., Yamasaki, E., Nishi, Y., Yamazaki, S., Azuma, T., Ito, Y., Ohtani, M., van der Wijk, T., den Hertog, J., Moss, J. and Hirayama, T. (2005) Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta, by Helicobacter pylori m2VacA. Cell. Microbiol. 7, 1285-1293

Jopling, C. and den Hertog, J. (2005) Fyn/Yes and non-canonical Wnt signaling converge on RhoA in vertebrate gastrulation cell movements. EMBO Rep. 6, 426 – 431

den Hertog, J. (2005) Chemical genetics: drug screens in zebrafish. Biosc. Rep., 25, 289-297

Groen, A., Lemeer, S., van der Wijk, T., Overvoorde, J., Heck, A.J.R., Ostman, A., Barford, D., Slijper, M., and den Hertog, J. (2005) Differential oxidation of protein-tyrosine phosphatases. J. Biol. Chem. 280, 10298-10304

den Hertog, J., Groen, A. and van der Wijk, T. (2005) Redox regulation of protein-tyrosine phosphatases. Arch. Biochem. Biophys. 434, 11-15

Bodrikov, V., Leshchyns’ka, I, Sytnyk, V., Overvoorde, J., den Hertog, J. and Schachner, M. (2005) RPTPalpha is essential for NCAM mediated p59fyn activation and neurite elongation. J. Cell Biol., 168, 127-139

van der Wijk, T., Blanchetot, C. and den Hertog, J (2005) Regulation of Receptor Protein-Tyrosine Phosphatase dimerization. Methods 35, 73-79

2004

Lorber, B., Berry, M., Hendriks, W., den Hertog, J., Pulido, R. and Logan, A. (2004) Stimulated regeneration of the crushed adult rat optic nerve correlates with attenuated expression of the protein tyrosine phosphatases RPTPalpha, STEP, and LAR. Mol. Cell. Neurosci. 27, 404-416

van der Wijk, T., Overvoorde, J. and den Hertog, J. (2004) H2O2 induced intermolecular disulfide bond formation between Receptor Protein-Tyrosine Phosphatases. J. Biol. Chem., 279, 44355-44361

Persson, C., Sjöblom, T., Groen, A., Kappert, K., Engström, U., Hellman, U., Heldin, C.H., den Hertog, J. and Östman, A. (2004) Preferential oxidation of the second phosphatase domain of receptor-like PTP-revealed by an antibody against oxidized protein tyrosine phosphatases. Proc. Natl. Acad. Sci. USA, 101, 1886-1891

den Hertog, J. (2004) Receptor Protein-Tyrosine Phosphatases. in: Top. Curr. Genet. (eds. J. Arino and D. Alexander) 17, 253-274

2003

den Hertog, J. (2003) Regulation of protein phosphatases in disease and behaviour. EMBO Rep. 4, 1027-1032

van der Wijk, T., Blanchetot, C., Overvoorde, J. and den Hertog, J. (2003) Redox-regulated rotational coupling of Receptor Protein-Tyrosine Phosphatase α dimers. J. Biol. Chem. 278,13968-13974

Toledano-Katchalski, H., Tiran, Z., Sines, T., Shani, G., Granot-Attas, S., den Hertog, J. and Elson, A. (2003) Dimerization in vivo and inhibition of the non-receptor form of protein tyrosine phosphatase Epsilon. Mol. Cell. Biol., 23, 5460-5471

Bink, R.J., Habuchi, H., Lele, Z., Dolk, E., Joore, J., Rauch, G.J., Geisler, R., Wilson, S., den Hertog, J., Kimata, K. and Zivkovic, D. (2003) Heparan sulfate 6-O-sulfotransferase is essential for muscle development in Zebrafish.
J. Biol. Chem., 278, 31118-31127

den Hertog, J., van der Wijk, T., Tertoolen, L.G.J. and Blanchetot, C. (2003) Receptor Protein-Tyrosine Phosphatase dimerization. in: Meth. Enzymol. (eds. S. Klumpp and J. Krieglstein) 366, 224-240

2002

Blanchetot, C., Tertoolen, L.G., and den Hertog, J. (2002). Regulation of Receptor Protein Tyrosine Phosphatase alpha by oxidative stress. EMBO J., 21, 493-503

van der Sar, A., Zivkovic, D., and den Hertog, J. (2002). Eye defects in receptor protein-tyrosine phosphatase alpha knock-down zebrafish. Dev.Dyn., 223, 292-297

Blanchetot, C., Tertoolen, L.G., Overvoorde, J. and den Hertog, J. (2002) Intra- and inter-molecular interactions between intracellular domains of Receptor Protein-Tyrosine Phosphatases. J. Biol. Chem., 277, 47263-47269

Gross, S., Blanchetot, C., Schepens, J., Albet, S., Lammers, R., den Hertog, J. and Hendriks, W. (2002). Multimerization of the protein tyrosine phosphatase-like IDDM autoantigens IA-2 and IA-2β with receptor PTPs: inhibition of RPTPα enzymatic activity. J. Biol. Chem., 277, 48139-48145

Rohn, J.L., Zhang, Y.H., Aalbers, R.I.J.M., Otto, N., den Hertog, J., Henriquez, N.V., van de Velde, C.J.H., Kuppen, P.J.K., Mumberg, D., Donner, P. and Noteborn, M.H.M. (2002) A tumor-specific kinase activity regulates the viral death protein Apoptin. J. Biol. Chem., 277, 50820-50827

2001

Tertoolen, L.G., Blanchetot, C., Jiang, G., Overvoorde, J., Gadella, T.W.J., Hunter, T., and den Hertog, J. (2001). Dimerization of Receptor Protein-Tyrosine Phosphatase alpha in living cells. BMC.Cell Biol. 2, 8

van der Sar, A., Betist, M., de Fockert, J., Overvoorde, J., Zivkovic, D., and den Hertog, J. (2001). Expression of receptor protein-tyrosine phosphatase alpha, sigma and LAR during development of the zebrafish embryo. Mech.Dev. 109, 423-426.

2000

Blanchetot, C. and den Hertog, J. (2000). Antibody-induced dimerization of HARPTPalpha-EGFR chimera suggests a ligand dependent mechanism of regulation for RPTPalpha. FEBS Lett. 484, 235-240.

Blanchetot, C. and den Hertog, J. (2000). Multiple interactions between receptor protein-tyrosine phosphatase (RPTP) alpha and membrane-distal protein-tyrosine phosphatase domains of various RPTPs. J.Biol.Chem. 275, 12446-12452.

Buist, A., Blanchetot, C., and den Hertog, J. (2000). Involvement of the membrane distal catalytic domain in pervanadate-induced tyrosine phosphorylation of receptor protein-tyrosine phosphatase alpha. Biochem. Biophys. Res. Commun. 267, 96-102.

Buist, A., Blanchetot, C., Tertoolen, L.G., and den Hertog, J. (2000). Identification of p130cas as an in vivo substrate of receptor protein-tyrosine phosphatase alpha. J.Biol.Chem. 275, 20754-20761.

Jiang, G., den Hertog, J., and Hunter, T. (2000). Receptor-like protein tyrosine phosphatase alpha homodimerizes on the cell surface. Mol.Cell Biol. 20, 5917-5929.

1999

Buist, A., Zhang, Y.L., Keng, Y.F., Wu, L., Zhang, Z.Y., and den Hertog, J. (1999). Restoration of potent protein-tyrosine phosphatase activity into the membrane-distal domain of receptor protein-tyrosine phosphatase alpha. Biochemistry 38, 914-922.

de Laat, S.W., Boonstra, J., Defize, L.H., Kruijer, W., van der Saag, P.T., Tertoolen, L.G., van Zoelen, E.J., and den Hertog, J. (1999). Growth factor signalling. Int.J.Dev.Biol. 43, 681-691.

den Hertog, J. (1999). Protein-tyrosine phosphatases in development. Mech.Dev. 85, 3-14.

den Hertog, J., Blanchetot, C., Buist, A., Overvoorde, J., van der Sar, A., and Tertoolen, L.G. (1999). Receptor protein-tyrosine phosphatase signalling in development. Int.J.Dev.Biol. 43, 723-733.

Jiang, G., den Hertog, J., Su, J., Noel, J., Sap, J., and Hunter, T. (1999). Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha. Nature 401, 606-610.

Kester, H.A., Blanchetot, C., den Hertog, J., van der Saag, P.T., and van der Burg, B. (1999). Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J.Biol.Chem. 274, 27439-27447.

van der Sar, A.M., de Fockert, J., Betist, M., Zivkovic, D., and den Hertog, J. (1999). Pleiotropic effects of zebrafish protein-tyrosine phosphatase-1B on early embryonic development. Int.J.Dev.Biol. 43 , 785-794.

Verheijen, M.H., Wolthuis, R.M., Defize, L.H., den Hertog, J., and Bos, J.L. (1999). Interdependent action of RalGEF and Erk in Ras-induced primitive endoderm differentiation of F9 embryonal carcinoma cells. Oncogene 18, 4435-4439.

1998

Buist, A., Tertoolen, L.G., and den Hertog, J. (1998). Potentiation of G-protein-coupled receptor-induced MAP kinase activation by exogenous EGF receptors in SK-N-MC neuroepithelioma cells. Biochem. Biophys. Res. Commun. 251, 6-10.

1997

van Puijenbroek, A.A., van Weering, D.H., van den Brink, C.E., Bos, J.L., van der Saag, P.T., de Laat, S.W., and den Hertog, J. (1997). Cell scattering of SK-N-MC neuroepithelioma cells in response to Ret and FGF receptor tyrosine kinase activation is correlated with sustained ERK2 activation. Oncogene 14, 1147-1157.

Wu, L., Buist, A., den Hertog, J., and Zhang, Z.Y. (1997). Comparative kinetic analysis and substrate specificity of the tandem catalytic domains of the receptor-like protein-tyrosine phosphatase alpha. J.Biol.Chem. 272, 6994-7002.

1996

Ameerun, R.F., de Winter, J.P., van den Eijnden-van Raaij, A.J., den Hertog, J., de Laat, S.W., and Tertoolen, L.G. (1996). Activin and basic fibroblast growth factor regulate neurogenesis of murine embryonal carcinoma cells. Cell Growth Differ. 7, 1679-1688.

Bilwes, A.M., den Hertog, J., Hunter, T., and Noel, J.P. (1996). Structural basis for inhibition of receptor protein-tyrosine phosphatase-alpha by dimerization. Nature 382, 555-559.

den Hertog, J. and Hunter, T. (1996). Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the SH2 and C-terminal SH3 domains. EMBO J. 15, 3016-3027.

den Hertog, J., Overvoorde, J., and de Laat, S.W. (1996). Expression of receptor protein-tyrosine phosphatase alpha mRNA and protein during mouse embryogenesis. Mech.Dev. 58, 89-101.

1995

Chen, L., Wu, L., Otaka, A., Smyth, M.S., Roller, P.P., Burke, T.R.J., den Hertog, J., and Zhang, Z.Y. (1995). Why is phosphonodifluoromethyl phenylalanine a more potent inhibitory moiety than phosphonomethyl phenylalanine toward protein-tyrosine phosphatases? Biochem. Biophys. Res. Commun. 216, 976-984.

den Hertog, J., Sap, J., Pals, C.E., Schlessinger, J., and Kruijer, W. (1995). Stimulation of receptor protein-tyrosine phosphatase alpha activity and phosphorylation by phorbol ester. Cell Growth Differ. 6, 303-307.

1994

den Hertog, J., Tracy, S., and Hunter, T. (1994). Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo. EMBO J. 13, 3020-3032.

den Hertog, J. and Kruijer, W. (1994). Receptor protein-tyrosine phosphatase alpha: regulation by phosphorylation and involvement in neuronal differentiation. Adv.Prot.Phosphat. 8, 311-324.

1993

de Groot, R.P., den Hertog, J., Vandenheede, J.R., Goris, J., and Sassone-Corsi, P. (1993). Multiple and cooperative phosphorylation events regulate the CREM activator function. EMBO J. 12, 3903-3911.

den Hertog, J., Pals, C.E., Peppelenbosch, M.P., Tertoolen, L.G., de Laat, S.W., and Kruijer, W. (1993). Receptor protein tyrosine phosphatase alpha activates pp60c-src and is involved in neuronal differentiation. EMBO J. 12, 3789-3798.

1992

de Laat, S.W., de Groot, R.P., den Hertog, J., Rijken, P.J., Verkleij, A.J., Kruijer, W., and Boonstra, J. (1992). Epidermal growth factor induced signal transduction in A431 cells is influenced by altered gravity conditions. Physiologist. 35, S19-S22

den Hertog, J., de Groot, R.P., de Laat, S.W., and Kruijer, W. (1992). EGF-induced jun B-expression in transfected P19 embryonal carcinoma cells expressing EGF-receptors is dependent on Jun D. Nucleic.Acids.Res. 20, 125-130.

den Hertog, J., Pals, C.E., Jonk, L.J., and Kruijer, W. (1992). Differential expression of a novel murine non-receptor protein tyrosine phosphatase during differentiation of P19 embryonal carcinoma cells. Biochem. Biophys. Res. Commun. 184, 1241-1249.

Peppelenbosch, M.P., Tertoolen, L.G., den Hertog, J., and de Laat, S.W. (1992). Epidermal growth factor activates calcium channels by phospholipase A2/5-lipoxygenase-mediated leukotriene C4 production. Cell 69, 295-303.

1991

de Groot, R.P., Rijken, P.J., den Hertog, J., Boonstra, J., Verkleij, A.J., de Laat, S.W., and Kruijer, W. (1991). Nuclear responses to protein kinase C signal transduction are sensitive to gravity changes. Exp.Cell Res. 197, 87-90.

den Hertog, J., de Laat, S.W., Schlessinger, J., and Kruijer, W. (1991). Neuronal differentiation in response to epidermal growth factor of transfected murine P19 embryonal carcinoma cells expressing human epidermal growth factor receptors. Cell Growth Differ. 2, 155-164.

den Hertog, J., Eman, R., Tertoolen, L.G., de Laat, S.W., and Kruijer, W. (1991). Characterization of a tyrosine kinase signaling pathway in undifferentiated P19 embryonal carcinoma cells. Exp.Cell Res. 196, 226-232.

Shen, S., Kruyt, F.A., den Hertog, J., van der Saag, P.T., and Kruijer, W. (1991). Mouse and human retinoic acid receptor beta 2 promoters: sequence comparison and localization of retinoic acid responsiveness. DNA Seq. 2, 111-119.

1990

de Groot, R.P., Rijken, P.J., den Hertog, J., Boonstra, J., Verkleij, A.J., de Laat, S.W., and Kruijer, W. (1990). Microgravity decreases c-fos induction and serum response element activity. J.Cell Sci. 97, 33-38.