A novel modular mosaic of cell adhesion motifs in the extracellular domains of the neurogenic trk and trkB tyrosine kinase receptors.
The extracellular domains of the human trk protooncogene and the closely homologous murine trkB share two highly conserved regions as well as several invariant cysteines which are supposed to be important for ligand recognition. Detailed comparative sequence analyses have now revealed the presence of a novel combination of distinct cell adhesion motifs corresponding precisely with these conserved regions. The N-terminal part consists of an array of three tandem leucine-rich motifs of 24 amino acids which is flanked by two distinct cysteine clusters. Significantly homologous structural features are found in the toll gene product of Drosophila, a transmembrane protein mediating specific cell adhesion events involved in the dorsoventral embryonic pattern formation. Directly adjacent to these structures we additionally identified two repeats of the immunoglobulin-like C2 type, which are significantly similar to repeats found in the neural cell adhesion molecules (N-CAMs) and in the platelet-derived growth factor receptor (PDGFR)-like tyrosine kinase receptor family. Our findings indicate that the trk/trkB protein tyrosine kinase receptors are involved in the transmembrane signalling of growth factor binding as well as of specific cell adhesion events during neuronal development. Additionally, we propose that the specifically expressed truncated forms of the trkB receptor, lacking the tyrosine kinase domain, are functioning as neural cell adhesion molecules. The knowledge of this domain structure will facilitate the elucidation of the molecular reasons why alterations in the extracellular region lead to oncogenic activation of the human trk proto-oncogene, which is a major cause of papillary thyroid carcinoma.
Schneider
R
R
Institut für Biochemie, Universität Innsbruck, Austria.
Schweiger
M
M
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D016384:Consensus Sequence; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009030:Mosaicism / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D020917:Receptor, trkA; D020813:Receptor, trkB; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*
C000715470:MAS1 protein, human; D008562:Membrane Glycoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB