An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors.
Mammalian cells constantly monitor and respond to a myriad of extracellular signals, often by using cell surface receptors. Two important classes of cell surface receptors include the receptor tyrosine kinases, which recognize peptide growth factors such as insulin, and the integrins, which most often mediate binding to components of the extracellular matrix. We report that the collagens serve as ligands for the previously orphan family of discoidin domain-containing receptor-like tyrosine kinases. The unexpected realization that an extracellular matrix molecule can directly serve as a ligand for receptor tyrosine kinases provides an example of ligands shared by integrins and receptor tyrosine kinases, and this finding seems likely to change prevailing views about the mechanisms by which cells perceive and respond to the extracellular matrix.
Shrivastava
Ajay
A
Begeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
Radziejewski
Czeslaw
C
Campbell
Ernest
E
Kovac
Lubomir
L
McGlynn
Marion
M
Ryan
Terence E
TE
Davis
Sam
S
Goldfarb
Mitchel P
MP
Glass
David J
DJ
Lemke
Greg
G
Yancopoulos
George D
GD
D000818:Animals; D019556:COS Cells; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D000070818:Discoidin Domain Receptors; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D010766:Phosphorylation; D010957:Plasmids; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012208:Rhabdomyosarcoma; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
C102893:DDR2 protein, S cerevisiae; D016326:Extracellular Matrix Proteins; D005656:Fungal Proteins; D016023:Integrins; D008024:Ligands; D011975:Receptors, Mitogen; D029701:Saccharomyces cerevisiae Proteins; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases