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PMID: 9659899 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The discoidin domain receptor tyrosine kinases are activated by collagen.

Molecular cell ·Vol. 1 ·No. 1 ·1997-12-00 ·Pages 13-23

Vogel W, Gish GD, Alves F, Pawson T

Abstract

Two mammalian receptor tyrosine kinases (DDR1 and DDR2) have extracellular domains closely related to a D. discoideum lectin, discoidin, required for cell aggregation. Here, we show that the mammalian DDR receptors bind and are activated by specific types of collagen. Stimulation of DDR receptor tyrosine kinase activity requires the native triple-helical structure of collagen and occurs over an extended period of time. Collagen activation of DDR1 induces phosphorylation of a docking site for the Shc phosphotyrosine binding domain, whose presence is controlled by alternative splicing. Activation of DDR2 by collagen results in the up-regulation of matrix metalloproteinase-1 expression. These results suggest that the discoidin-related DDR tyrosine kinases are novel collagen receptors with the potential to control cellular responses to the extracellular matrix.

MeSH Terms

Amino Acid Sequence Animals Binding Sites/drug effects,physiology Biocompatible Materials Breast Neoplasms Carbohydrate Metabolism Carbohydrates/chemistry Collagen/metabolism,pharmacology Collagenases/biosynthesis,pharmacology Discoidin Domain Receptors Drug Combinations Extracellular Matrix Proteins/metabolism,pharmacology Fibroblasts/chemistry,cytology,enzymology Fibrosarcoma Hot Temperature Humans Kidney/cytology Kinetics Laminin Ligands Matrix Metalloproteinase 1 Mice Molecular Sequence Data Pepsin A/pharmacology Phosphorylation Protein Denaturation Protein Structure, Tertiary Proteoglycans Receptor Protein-Tyrosine Kinases/chemistry,metabolism Receptors, Mitogen/chemistry,metabolism Tendons/chemistry Tumor Cells, Cultured/chemistry,drug effects,enzymology Tyrosine/metabolism

Chemicals

Biocompatible Materials Carbohydrates Drug Combinations Extracellular Matrix Proteins Laminin Ligands Proteoglycans Receptors, Mitogen matrigel Tyrosine Collagen Discoidin Domain Receptors Receptor Protein-Tyrosine Kinases Pepsin A Collagenases Matrix Metalloproteinase 1

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Vogel W

Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Gish G D

Alves F

Pawson T

Article Info

Journal

Molecular cell

Abbr.

Mol Cell

ISSN

1097-2765

DOI

10.1016/s1097-2765(00)80003-9

Published

1997-12-00

Pages

13-23

Language

English

Region

United States

NLM ID

9802571

Subset

External Links

PubMed source DOI: 10.1016/s1097-2765(00)80003-9 View journal details

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