Biomedical subjects

Marta Rosário

Publications and source records attributed to Marta Rosário.

4 recordsLinked to original sources

PubMed2005

Balancing cell adhesion and Wnt signaling, the key role of beta-catenin.

Controlled regulation of cell proliferation and differentiation is essential for embryonic development and requires the coordinated regulation of cell-cell adhesion and gene transcription. The armadillo repeat protein beta-catenin is an important integrator of both processes. Beta-catenin acts in the Wnt signaling pathway, activating the transcription of crucial target genes responsible for cellular proliferation and differentiation. Beta-catenin also controls E-cadherin-mediated cell adhesion at the plasma membrane and mediates the interplay of adherens junction molecules with the actin cytoskeleton. Both functions of beta-catenin are de-regulated in human malignancies, thereby leading both to the loss of cell-cell adhesion and to the increased transcription of Wnt target genes.

Amino Acid Sequence↗

PubMed2004

The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells.

Shank proteins, initially also described as ProSAP proteins, are scaffolding adaptors that have been previously shown to integrate neurotransmitter receptors into the cortical cytoskeleton at postsynaptic densities. We show here that Shank proteins are also crucial in receptor tyrosine kinase signaling. The PDZ domain-containing Shank3 protein was found to represent a novel interaction partner of the receptor tyrosine kinase Ret, which binds specifically to a PDZ-binding motif present in the Ret9 but not in the Ret51 isoform. Furthermore, we show that Ret9 but not Ret51 induces epithelial cells to form branched tubular structures in three-dimensional cultures in a Shank3-dependent manner. Ret9 but not Ret51 has been previously shown to be required for kidney development. Shank3 protein mediates sustained Erk-MAPK and PI3K signaling, which is crucial for tubule formation, through recruitment of the adaptor protein Grb2. These results demonstrate that the Shank3 adaptor protein can mediate cellular signaling, and provide a molecular mechanism for the biological divergence between the Ret9 and Ret51 isoform.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Making tubes: step by step.

Branched hollow tubes form the architectural basis of many mammalian organs. The growth factor HGF/SF and its receptor, the Met receptor tyrosine kinase, stimulate epithelial cells to undergo tubulogenesis in vitro. In this issue of Developmental Cell, O'Brien et al. (2004) look at temporal regulation and the role of two HGF/SF effectors, the ERK 1/2 MAP kinases and matrix metalloproteases, in this process.

Animals↗

PubMed2003

How to make tubes: signaling by the Met receptor tyrosine kinase.

Hepatocyte growth factor/scatter factor (HGF/SF), acting through the receptor tyrosine kinase Met, stimulates cells derived from a variety of different organs to form elongated hollow tubules when grown in three-dimensional gels. In vivo data also indicate a role for HGF/SF and Met in tubule formation during liver and kidney regeneration and mammary gland formation. Activation of Met results in the recruitment of a myriad of signal transducers that regulate dissociation of adherens junctions and the stimulation of cellular motility, survival, proliferation and morphogenesis during tubule formation. Among these many signal transducers, the Gab1 adaptor protein and its effector, the SHP2 tyrosine phosphatase, have been found to be crucial for tubulogenesis and for the sustained stimulation of the ERK/MAP kinase pathway. Here, we discuss the contribution of these and other signaling pathways and the role of HGF/SF and Met in the formation of epithelial cell tubules both in vitro in branching-morphogenesis assays and in vivo during organogenesis.

Animals↗