Research groups
News & events
Jobs & education

Research objectives

Protein-tyrosine phosphatases in development

Protein phosphorylation on tyrosine residues is an important cell signalling mechanism that has a pivotal role in many biological processes. Cellular protein phosphotyrosine levels are 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 signalling. Using biochemical and cell biological approaches, we study PTP-signalling in order to obtain insight into conceptual questions about substrates, regulation, ligands and effectors. In recent years, we found that the proto-typical RPTPalpha is regulated by dimerization, oxidation and phosphorylation.

We use the zebrafish to elucidate the role of PTPs and PTKs in early vertebrate development. Recently, we found that the PTKs, Fyn and Yes, have an important role in convergence and extension cell movements in zebrafish gastrulation, signaling in parallel to non-canonical Wnts, upstream of the small GTPase, RhoA. Moreover, we found that the PTP, Shp2, is essential for normal convergence and extension cell movements. Expression of mutant Shp2 with mutations that were identified in human Noonan or LEOPARD syndrome resulted in impaired cell movements during gastrulation and the phenotype was reminiscent of the symptoms in human patients, including cardiac and craniofacial defects.

PTEN is a tumor suppressor gene that belongs to the PTP superfamily and exhibits lipid phosphatase activity with high selectivity for the 3-position of phosphatidylinositol(3,4,5)trisphosphate. The zebrafish genome encodes two pten genes, ptena and ptenb. We isolated null mutants of both pten genes and found that zebrafish with a single wild type pten allele develop hemangiosarcomas. Double homozygous ptena-/-ptenb-/- mutant embryos are embryonic lethal and display a pleiotropic phenotype, including hyperproliferation of endothelial cells, resulting in hyperbranching of blood vessels. Hematopoiesis is also affected in ptena-/-ptenb-/- mutants, in that hematopoietic stem and progenitor cells (HSPCs) hyperproliferate and arrest in differentiation in embryos lacking functional Pten.

About the group leader
Publication list




image description




image description






image description