Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jun 15, 1993; 90(12): 5677–5681.

A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain.


We have identified a breast carcinoma tyrosine phosphoprotein, discoidin domain receptor (DDR), that defines an unusual class of receptor tyrosine kinases. The DDR cDNA predicts a C-terminal tyrosine kinase domain and an N-terminal domain similar to the Dictyostelium discoideum lectin discoidin I. These domains are connected by an extraordinary hydrophilic proline/glycine-rich domain, which is interrupted by a predicted transmembrane sequence. This extended proline/glycine-rich region may be required for an unusual geometry of interaction with ligand or substrates. Discoidin I domains are also found in other proteins, including coagulation factors V and VIII, and may represent a class of domains that interact with specific cell surface molecules.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bishop JM. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. [PubMed]
  • Hunter T. Protein kinase classification. Methods Enzymol. 1991;200:3–37. [PubMed]
  • Hanks SK, Quinn AM. Protein kinase catalytic domain sequence database: identification of conserved features of primary structure and classification of family members. Methods Enzymol. 1991;200:38–62. [PubMed]
  • Shier P, Watt VM. Primary structure of a putative receptor for a ligand of the insulin family. J Biol Chem. 1989 Sep 5;264(25):14605–14608. [PubMed]
  • Gubler U, Hoffman BJ. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. [PubMed]
  • Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA, Rutter WJ. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987 Sep 24;329(6137):301–307. [PubMed]
  • Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. [PMC free article] [PubMed]
  • Ellis L, Clauser E, Morgan DO, Edery M, Roth RA, Rutter WJ. Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose. Cell. 1986 Jun 6;45(5):721–732. [PubMed]
  • Kaufman RJ. Vectors used for expression in mammalian cells. Methods Enzymol. 1990;185:487–511. [PubMed]
  • Chen WJ, Goldstein JL, Brown MS. NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor. J Biol Chem. 1990 Feb 25;265(6):3116–3123. [PubMed]
  • Martin-Zanca D, Oskam R, Mitra G, Copeland T, Barbacid M. Molecular and biochemical characterization of the human trk proto-oncogene. Mol Cell Biol. 1989 Jan;9(1):24–33. [PMC free article] [PubMed]
  • Bansal A, Gierasch LM. The NPXY internalization signal of the LDL receptor adopts a reverse-turn conformation. Cell. 1991 Dec 20;67(6):1195–1201. [PubMed]
  • Springer WR, Cooper DN, Barondes SH. Discoidin I is implicated in cell-substratum attachment and ordered cell migration of Dictyostelium discoideum and resembles fibronectin. Cell. 1984 Dec;39(3 Pt 2):557–564. [PubMed]
  • Poole S, Firtel RA, Lamar E, Rowekamp W. Sequence and expression of the discoidin I gene family in Dictyostelium discoideum. J Mol Biol. 1981 Dec 5;153(2):273–289. [PubMed]
  • Kane WH, Davie EW. Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6800–6804. [PMC free article] [PubMed]
  • Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Buecker JL, Pittman DD, Kaufman RJ, Brown E, Shoemaker C, Orr EC, et al. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature. 1984 Nov 22;312(5992):342–347. [PubMed]
  • Vehar GA, Keyt B, Eaton D, Rodriguez H, O'Brien DP, Rotblat F, Oppermann H, Keck R, Wood WI, Harkins RN, et al. Structure of human factor VIII. Nature. 1984 Nov 22;312(5992):337–342. [PubMed]
  • Stubbs JD, Lekutis C, Singer KL, Bui A, Yuzuki D, Srinivasan U, Parry G. cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8417–8421. [PMC free article] [PubMed]
  • Larocca D, Peterson JA, Urrea R, Kuniyoshi J, Bistrain AM, Ceriani RL. A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains. Cancer Res. 1991 Sep 15;51(18):4994–4998. [PubMed]
  • Tracy PB, Peterson JM, Nesheim ME, McDuffie FC, Mann KG. Interaction of coagulation factor V and factor Va with platelets. J Biol Chem. 1979 Oct 25;254(20):10354–10361. [PubMed]
  • Nesheim ME, Pittman DD, Wang JH, Slonosky D, Giles AR, Kaufman RJ. The binding of 35S-labeled recombinant factor VIII to activated and unactivated human platelets. J Biol Chem. 1988 Nov 5;263(31):16467–16470. [PubMed]
  • Takagi S, Hirata T, Agata K, Mochii M, Eguchi G, Fujisawa H. The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron. 1991 Aug;7(2):295–307. [PubMed]
  • Takagi S, Tsuji T, Amagai T, Takamatsu T, Fujisawa H. Specific cell surface labels in the visual centers of Xenopus laevis tadpole identified using monoclonal antibodies. Dev Biol. 1987 Jul;122(1):90–100. [PubMed]
  • Robinson MS. Cloning of cDNAs encoding two related 100-kD coated vesicle proteins (alpha-adaptins). J Cell Biol. 1989 Mar;108(3):833–842. [PMC free article] [PubMed]
  • Ponnambalam S, Robinson MS, Jackson AP, Peiperl L, Parham P. Conservation and diversity in families of coated vesicle adaptins. J Biol Chem. 1990 Mar 25;265(9):4814–4820. [PubMed]
  • Kirchhausen T, Nathanson KL, Matsui W, Vaisberg A, Chow EP, Burne C, Keen JH, Davis AE. Structural and functional division into two domains of the large (100- to 115-kDa) chains of the clathrin-associated protein complex AP-2. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2612–2616. [PMC free article] [PubMed]
  • Robinson MS. Cloning and expression of gamma-adaptin, a component of clathrin-coated vesicles associated with the Golgi apparatus. J Cell Biol. 1990 Dec;111(6 Pt 1):2319–2326. [PMC free article] [PubMed]
  • Virshup DM, Bennett V. Clathrin-coated vesicle assembly polypeptides: physical properties and reconstitution studies with brain membranes. J Cell Biol. 1988 Jan;106(1):39–50. [PMC free article] [PubMed]
  • Heuser JE, Keen J. Deep-etch visualization of proteins involved in clathrin assembly. J Cell Biol. 1988 Sep;107(3):877–886. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...