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| Item Type: | Article |
|---|---|
| Title: | Motogenic and morphogenic activity of epithelial receptor tyrosine kinases |
| Creators Name: | Sachs, M. and Weidner, K.M. and Brinkmann, V. and Walther, I. and Obermeier, A. and Ullrich, A. and Birchmeier, W. |
| Abstract: | Receptor tyrosine kinases play essential roles in morphogenesis and differentiation of epithelia. Here we examined various tyrosine kinase receptors, which are preferentially expressed in epithelia (c-met, c-ros, c-neu, and the keratin growth factor [KGF] receptor), for their capacity to induce cell motility and branching morphogenesis of epithelial cells. We exchanged the ligand-binding domain of these receptors by the ectodomain of trkA and could thus control signaling by the new ligand, NGF. We demonstrate here that the tyrosine kinases of c-met, c-ros, c-neu, the KGF receptor, and trkA, but not the insulin receptor, induced scattering and increased motility of kidney epithelial cells in tissue culture. Mutational analysis suggests that SHC binding is essential for scattering and increased cell motility induced by trkA. The induction of motility in epithelial cells is thus an important feature of various receptor tyrosine kinases, which in vivo play a role in embryogenesis and metastasis. In contrast, only the c-met receptor promoted branching morphogenesis of kidney epithelial cells in three-dimensional matrices, which resemble the formation of tubular epithelia in development. Interestingly, the ability of c-met to induce morphogenesis could be transferred to trkA, when in a novel receptor hybrid COOH-terminal sequences of c-met (including Y14 to Y16) were fused to the trkA kinase domain. These data demonstrate that tubulogenesis of epithelia is a restricted activity of tyrosine kinases, as yet only demonstrated for the c-met receptor. We predict the existence of specific substrates that mediate this morphogenesis signal. |
| Keywords: | Amino Acid Sequence, Base Sequence, Cell Line, Cell Movement, DNA Primers, Epithelial Cells, Epithelium, Molecular Sequence Data, Molecular Structure, Morphogenesis, Nerve Growth Factor Receptors, Nerve Growth Factors, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-Met, Receptor Protein-Tyrosine Kinases, Recombinant DNA, Recombinant Fusion Proteins, Transfection, trkA Receptor, Animals, Dogs |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 133 |
| Number: | 5 |
| Page Range: | 1095-1107 |
| Date: | 3 June 1996 |
| Additional Information: | Copyright (c) 1996 by The Rockefeller University Press |
| Official Publication: | http://www.jcb.org/cgi/reprint/133/5/1095 |
| PubMed: | View item in PubMed |
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