mitogen receptors


Summary: Glycoprotein molecules on the surface of B- and T-lymphocytes, that react with molecules of antilymphocyte sera, lectins, and other agents which induce blast transformation of lymphocytes.

Top Publications

  1. Avivi Green C, Singal M, Vogel W. Discoidin domain receptor 1-deficient mice are resistant to bleomycin-induced lung fibrosis. Am J Respir Crit Care Med. 2006;174:420-7 pubmed
    ..DDR1 expression is a prerequisite for the development of lung inflammation and fibrosis. Blockade of DDR1 may therefore be a novel therapeutic intervention in patients with pulmonary fibrosis. ..
  2. Sturge J, Wienke D, Isacke C. Endosomes generate localized Rho-ROCK-MLC2-based contractile signals via Endo180 to promote adhesion disassembly. J Cell Biol. 2006;175:337-47 pubmed
    ..We propose migration driven by Endo180 as a model for the spatial regulation of contractility and adhesion dynamics by endosomes. ..
  3. Sturge J, Wienke D, East L, Jones G, Isacke C. GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis. J Cell Biol. 2003;162:789-94 pubmed
    ..From these studies, we conclude that Endo180 is a crucial link between uPA-uPAR and setting of the internal cellular compass. ..
  4. Yang K, Kim J, Kim H, Park I, Kim I, Yang B. Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src stimulates intramolecular autophosphorylation and Shc signaling complex formation. J Biol Chem. 2005;280:39058-66 pubmed
  5. Mao T, Kimura Y, Kenny T, Branchi A, Gishi R, Van de Water J, et al. Elevated expression of tyrosine kinase DDR2 in primary biliary cirrhosis. Autoimmunity. 2002;35:521-9 pubmed
    ..Therefore, unusually high DDR2 expression in the bile ducts of PBC patients could contribute to duct injury by altering local cytokine levels and thereby increasing immune-mediated damage. ..
  6. Abdulhussein R, Koo D, Vogel W. Identification of disulfide-linked dimers of the receptor tyrosine kinase DDR1. J Biol Chem. 2008;283:12026-33 pubmed
    ..The identification of DDR1 dimers provides new insights into the molecular structure of receptor tyrosine kinases and suggests distinct signaling mechanisms of each receptor subfamily. ..
  7. Vogel W. Collagen-receptor signaling in health and disease. Eur J Dermatol. 2001;11:506-14 pubmed
    ..Some recently discovered mechanisms of locally controlled expression of collagen, collagen-binding receptors and collagen-degrading proteases in the cellular microenvironment are described. ..
  8. Ikeda K, Wang L, Torres R, Zhao H, Olaso E, Eng F, et al. Discoidin domain receptor 2 interacts with Src and Shc following its activation by type I collagen. J Biol Chem. 2002;277:19206-12 pubmed
    ..The data support a model in which Src and the DDR2 receptor cooperate in a regulated fashion to direct the phosphorylation of both the receptor and its targets. ..
  9. East L, Isacke C. The mannose receptor family. Biochim Biophys Acta. 2002;1572:364-86 pubmed
    ..In addition, they differ in their ability to mediate endocytic and phagocytic events and in their intracellular destinations. Together, they represent a unique group of multidomain, multifunctional receptors. ..

More Information


  1. Ichikawa O, Osawa M, Nishida N, Goshima N, Nomura N, Shimada I. Structural basis of the collagen-binding mode of discoidin domain receptor 2. EMBO J. 2007;26:4168-76 pubmed
    ..The surface profile of the collagen-binding site suggests that the DDR2-DS domain recognizes specific sites on fibrillar collagen. This study provides a molecular basis for the collagen-binding mode of the DDR2-DS domain. ..
  2. Wagenaar Miller R, Engelholm L, Gavard J, Yamada S, Gutkind J, Behrendt N, et al. Complementary roles of intracellular and pericellular collagen degradation pathways in vivo. Mol Cell Biol. 2007;27:6309-22 pubmed
    ..These findings have important implications for the use of pharmacological inhibitors of collagenase activity to prevent connective tissue destruction in a variety of diseases. ..
  3. Hoffmann S, Schellack C, Textor S, Konold S, Schmitz D, Cerwenka A, et al. Identification of CLEC12B, an inhibitory receptor on myeloid cells. J Biol Chem. 2007;282:22370-5 pubmed
  4. Engelholm L, List K, Netzel Arnett S, Cukierman E, Mitola D, Aaronson H, et al. uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion. J Cell Biol. 2003;160:1009-15 pubmed
    ..These studies identify a central function of uPARAP/Endo180 in cellular collagen interactions. ..
  5. Han Y, Zhang M, Li N, Chen T, Zhang Y, Wan T, et al. KLRL1, a novel killer cell lectinlike receptor, inhibits natural killer cell cytotoxicity. Blood. 2004;104:2858-66 pubmed
    ..Taken together, our results demonstrate that KLRL1 belongs to the KLR family and is a novel inhibitory NK cell receptor. ..
  6. Leitinger B, Steplewski A, Fertala A. The D2 period of collagen II contains a specific binding site for the human discoidin domain receptor, DDR2. J Mol Biol. 2004;344:993-1003 pubmed
    ..The discovery of a site-specific interaction of DDR2 with collagen II gives novel insight into the nature of the interaction of collagen II with matrix receptors. ..
  7. Bailey L, Wienke D, Howard M, Knauper V, Isacke C, Murphy G. Investigation of the role of Endo180/urokinase-type plasminogen activator receptor-associated protein as a collagenase 3 (matrix metalloproteinase 13) receptor. Biochem J. 2002;363:67-72 pubmed
    ..We conclude that Endo180 is unlikely to be a receptor for collagenase 3 in relation to either its activation or cell binding and internalization, and that other interaction partners must be sought. ..
  8. Engelholm L, Nielsen B, Netzel Arnett S, Solberg H, Chen X, Lopez Garcia J, et al. The urokinase plasminogen activator receptor-associated protein/endo180 is coexpressed with its interaction partners urokinase plasminogen activator receptor and matrix metalloprotease-13 during osteogenesis. Lab Invest. 2001;81:1403-14 pubmed
    ..The data suggest a function of this novel protease receptor in bone development, possibly mediated through its interactions with uPAR, MMP-13, or collagen V. ..
  9. Konitsiotis A, Raynal N, Bihan D, Hohenester E, Farndale R, Leitinger B. Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. J Biol Chem. 2008;283:6861-8 pubmed publisher
    ..Thus, DDR2 activation may be effected by single triple-helices rather than fibrillar collagen. ..
  10. Pyz E, Huysamen C, Marshall A, Gordon S, Taylor P, Brown G. Characterisation of murine MICL (CLEC12A) and evidence for an endogenous ligand. Eur J Immunol. 2008;38:1157-63 pubmed publisher
    ..Finally, we show that mMICL recognises an endogenous ligand in a variety of murine tissues, suggesting that the receptor plays a role in homeostasis. ..
  11. Vogel W, Brakebusch C, Fassler R, Alves F, Ruggiero F, Pawson T. Discoidin domain receptor 1 is activated independently of beta(1) integrin. J Biol Chem. 2000;275:5779-84 pubmed
    ..Finally, we show that overexpression of dominant negative DDR1 in the myoblast cell line C2C12 blocks cellular differentiation and the formation of myofibers. ..
  12. Bates E, Fournier N, Garcia E, Valladeau J, Durand I, Pin J, et al. APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif. J Immunol. 1999;163:1973-83 pubmed
    ..DCIR represents a novel surface molecule expressed by Ag presenting cells, and of potential importance in regulation of DC function. ..
  13. Mousavi S, Sato M, Sporstøl M, Smedsrød B, Berg T, Kojima N, et al. Uptake of denatured collagen into hepatic stellate cells: evidence for the involvement of urokinase plasminogen activator receptor-associated protein/Endo180. Biochem J. 2005;387:39-46 pubmed
    ..These results together suggest that uPARAP/Endo180 mediates endocytosis of collagen in rat liver stellate cells. ..
  14. Leitinger B, Hohenester E. Mammalian collagen receptors. Matrix Biol. 2007;26:146-55 pubmed
    ..In this review, we discuss the structure and function of these receptors, focussing on the principles involved in collagen recognition. ..
  15. Abdulhussein R, McFadden C, Fuentes Prior P, Vogel W. Exploring the collagen-binding site of the DDR1 tyrosine kinase receptor. J Biol Chem. 2004;279:31462-70 pubmed
  16. Marshall A, Willment J, Pyz E, Dennehy K, Reid D, Dri P, et al. Human MICL (CLEC12A) is differentially glycosylated and is down-regulated following cellular activation. Eur J Immunol. 2006;36:2159-69 pubmed
    ..This suggests that human MICL may be involved in the control of myeloid cell activation during inflammation. ..
  17. Carafoli F, Bihan D, Stathopoulos S, Konitsiotis A, Kvansakul M, Farndale R, et al. Crystallographic insight into collagen recognition by discoidin domain receptor 2. Structure. 2009;17:1573-1581 pubmed publisher
    ..A comparison of the GVMGFO-binding sites of DDR2 and SPARC reveals a striking case of convergent evolution in collagen recognition. ..
  18. Rivera Calzada A, Robertson D, MacFadyen J, Boskovic J, Isacke C, Llorca O. Three-dimensional interplay among the ligand-binding domains of the urokinase-plasminogen-activator-receptor-associated protein, Endo180. EMBO Rep. 2003;4:807-12 pubmed
    ..We show that for Endo180, the cysteine-rich domain contacts the second C-type lectin-like domain, thus providing structural insight into how modulation of its several ligand interactions may regulate Endo180 receptor function. ..
  19. Hou G, Vogel W, Bendeck M. Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression. Circ Res. 2002;90:1147-9 pubmed
    ..These results suggest that active DDR1 kinase is a central mediator of SMC migration. ..
  20. Bargal R, Cormier Daire V, Ben Neriah Z, Le Merrer M, Sosna J, Melki J, et al. Mutations in DDR2 gene cause SMED with short limbs and abnormal calcifications. Am J Hum Genet. 2009;84:80-4 pubmed publisher
    ..The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk...
  21. Howard M, Chambers M, Mason R, Isacke C. Distribution of Endo180 receptor and ligand in developing articular cartilage. Osteoarthritis Cartilage. 2004;12:74-82 pubmed
    ..In addition, our data indicates that Endo180 does not appear to play a role in the development or progression of murine osteoarthritis. ..
  22. Wienke D, MacFadyen J, Isacke C. Identification and characterization of the endocytic transmembrane glycoprotein Endo180 as a novel collagen receptor. Mol Biol Cell. 2003;14:3592-604 pubmed
  23. Wienke D, Davies G, Johnson D, Sturge J, Lambros M, Savage K, et al. The collagen receptor Endo180 (CD280) Is expressed on basal-like breast tumor cells and promotes tumor growth in vivo. Cancer Res. 2007;67:10230-40 pubmed
    ..Together, these data argue that elevated expression of this receptor in tumor cells could have important consequences in subsets of basal-like carcinomas for which there is a current lack of effective treatment. ..
  24. Sulek J, Wagenaar Miller R, Shireman J, Molinolo A, Madsen D, Engelholm L, et al. Increased expression of the collagen internalization receptor uPARAP/Endo180 in the stroma of head and neck cancer. J Histochem Cytochem. 2007;55:347-53 pubmed
    ..These data suggest that uPARAP/Endo180 participates in the connective tissue destruction during head and neck squamous cell carcinoma progression by mediating cellular uptake and lysosomal degradation of collagen. ..
  25. Leitinger B. Molecular analysis of collagen binding by the human discoidin domain receptors, DDR1 and DDR2. Identification of collagen binding sites in DDR2. J Biol Chem. 2003;278:16761-9 pubmed
    ..In addition, the same loops were required for collagen-dependent receptor activation. It is concluded that the loop region opposite to the polypeptide chain termini of the DDR2 discoidin domain constitutes the collagen recognition site. ..
  26. Hou G, Vogel W, Bendeck M. The discoidin domain receptor tyrosine kinase DDR1 in arterial wound repair. J Clin Invest. 2001;107:727-35 pubmed
    ..Our results support the hypothesis that DDR1 plays an important role as a collagen receptor, mediating intimal thickening after vascular injury. ..
  27. Boyington J, Riaz A, Patamawenu A, Coligan J, Brooks A, Sun P. Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors. Immunity. 1999;10:75-82 pubmed
    ..The formation of this dimer reveals a putative ligand-binding region for HLA-E and suggests how NKG2 interacts with CD94. ..
  28. Vogel W, Abdulhussein R, Ford C. Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal. 2006;18:1108-16 pubmed
    ..By highlighting current questions about these unusual collagen receptors, we hope to attract new research on DDRs from a variety of different fields. ..
  29. Leitinger B, Kwan A. The discoidin domain receptor DDR2 is a receptor for type X collagen. Matrix Biol. 2006;25:355-64 pubmed
    ..Our study is the first to describe a non-fibrillar collagen ligand for DDR2 and will form the basis for further studies into the biological function of collagen X during endochondral ossification. ..
  30. Llorca O. Extended and bent conformations of the mannose receptor family. Cell Mol Life Sci. 2008;65:1302-10 pubmed publisher
    ..Conformational transitions between these two states seem to regulate the interaction of these receptors with ligands and their oligomerization. ..
  31. Farndale R, Lisman T, Bihan D, Hamaia S, Smerling C, Pugh N, et al. Cell-collagen interactions: the use of peptide Toolkits to investigate collagen-receptor interactions. Biochem Soc Trans. 2008;36:241-50 pubmed publisher
    ..Thus the availability of extracellular collagen-binding proteins may be important in regulating and facilitating direct collagen-receptor interaction. ..
  32. Lee R, Eidman K, Kren S, Hostetter T, Segal Y. Localization of discoidin domain receptors in rat kidney. Nephron Exp Nephrol. 2004;97:e62-70 pubmed
    ..Upregulation within glomeruli of remnant kidneys suggests the possibility of additional roles in kidney injury. The DDR2 localization in adult rat kidneys is inconsistent with roles in cell-matrix interactions. ..
  33. Nemoto T, Ohashi K, Akashi T, Johnson J, Hirokawa K. Overexpression of protein tyrosine kinases in human esophageal cancer. Pathobiology. 1997;65:195-203 pubmed
    ..In addition, we confirmed the expression of two isoforms of DDR/trkE/Cak in normal and cancerous esophagus. Our study suggests that DDR/trkE/Cak plays an important role in the regulation of proliferation of esophageal cancer. ..
  34. East L, Rushton S, Taylor M, Isacke C. Characterization of sugar binding by the mannose receptor family member, Endo180. J Biol Chem. 2002;277:50469-75 pubmed
    ..Thus, although Endo180 and the mannose receptor are now both known to be mannose binding lectins, each receptor is likely to have a distinct set of glycoprotein ligands in vivo. ..
  35. Behrendt N. The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180): membrane proteins engaged in matrix turnover during tissue remodeling. Biol Chem. 2004;385:103-36 pubmed
    ..Both receptors have additional functions that are currently being unraveled. The present discussion of uPAR and uPARAP is centered on their protein structure and molecular and cellular function. ..
  36. Ram R, Lorente G, Nikolich K, Urfer R, Foehr E, Nagavarapu U. Discoidin domain receptor-1a (DDR1a) promotes glioma cell invasion and adhesion in association with matrix metalloproteinase-2. J Neurooncol. 2006;76:239-48 pubmed
    ..These results suggest that DDR1a plays a critical role in inducing tumor cell adhesion and invasion, and this invasive phenotype is caused by activation of matrix metalloproteinase-2. ..
  37. Huysamen C, Willment J, Dennehy K, Brown G. CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes. J Biol Chem. 2008;283:16693-701 pubmed publisher
    ..These data indicate that CLEC9A functions as an activation receptor. ..
  38. Weiner H, Huang H, Zagzag D, Boyce H, Lichtenbaum R, Ziff E. Consistent and selective expression of the discoidin domain receptor-1 tyrosine kinase in human brain tumors. Neurosurgery. 2000;47:1400-9 pubmed
    ..The expression of DDR1 by tumor cells of CNS neoplasms and by primitive cells of the embryonic ventricular zone suggests that DDR1 is a potentially useful marker of tumor cells within the CNS. ..
  39. Howard M, Isacke C. The C-type lectin receptor Endo180 displays internalization and recycling properties distinct from other members of the mannose receptor family. J Biol Chem. 2002;277:32320-31 pubmed
    ..These findings demonstrate that despite an overall structural similarity, members of this receptor family employ distinct trafficking mechanisms that may reflect important differences in their physiological functions. ..
  40. Marshall A, Willment J, Lin H, Williams D, Gordon S, Brown G. Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is predominantly expressed on granulocytes and monocytes. J Biol Chem. 2004;279:14792-802 pubmed
    ..These data suggest that MICL is a negative regulator of granulocyte and monocyte function. ..
  41. del Pino E, Cabada M. Lectin binding sites in the vitelline envelope of Bufo arenarum oocytes: role in fertilization. Gamete Res. 1987;17:333-42 pubmed
  42. Sturge J, Todd S, Kogianni G, McCarthy A, Isacke C. Mannose receptor regulation of macrophage cell migration. J Leukoc Biol. 2007;82:585-93 pubmed
    ..As MR is down-regulated during macrophage activation, these findings have implications for the regulation of macrophage migration during different stages of pathogenesis. ..
  43. Ferri N, Carragher N, Raines E. Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis. Am J Pathol. 2004;164:1575-85 pubmed
    ..Taken together, these data provide evidence for the potential roles of DDR1 and DDR2 in the regulation of collagen turnover mediated by SMCs in obstructive diseases of blood vessels and the lung. ..
  44. Sheikh H, Yarwood H, Ashworth A, Isacke C. Endo180, an endocytic recycling glycoprotein related to the macrophage mannose receptor is expressed on fibroblasts, endothelial cells and macrophages and functions as a lectin receptor. J Cell Sci. 2000;113 ( Pt 6):1021-32 pubmed
  45. Sancho D, Mourão Sá D, Joffre O, Schulz O, Rogers N, Pennington D, et al. Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin. J Clin Invest. 2008;118:2098-110 pubmed publisher
    ..We conclude that DNGR-1 is a novel, highly specific marker of mouse and human DC subsets that can be exploited for CTL cross-priming and tumor therapy. ..
  46. East L, McCarthy A, Wienke D, Sturge J, Ashworth A, Isacke C. A targeted deletion in the endocytic receptor gene Endo180 results in a defect in collagen uptake. EMBO Rep. 2003;4:710-6 pubmed
  47. Labrador J, Azcoitia V, Tuckermann J, Lin C, Olaso E, Manes S, et al. The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism. EMBO Rep. 2001;2:446-52 pubmed
    ..Together our results suggest that DDR2 acts as an extracellular matrix sensor to modulate cell proliferation. ..
  48. Wall S, Werner E, Werb Z, DeClerck Y. Discoidin domain receptor 2 mediates tumor cell cycle arrest induced by fibrillar collagen. J Biol Chem. 2005;280:40187-94 pubmed
    ..Our data provide evidence for a novel direct mechanism by which cell contact with fibrillar collagen restricts proliferation. ..
  49. Vogel W, Gish G, Alves F, Pawson T. The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell. 1997;1:13-23 pubmed
    ..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. ..
  50. Chen C, Floyd H, Olson N, Magaletti D, Li C, Draves K, et al. Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production. Blood. 2006;107:1459-67 pubmed
    ..Thus, DCAL-2 may program DCs differently depending on whether DCs are signaled via TLRs or by T cells. DCAL-2 may be a potential immunotherapeutic target for modulating autoimmune diseases or for developing vaccines. ..
  51. Honardoust H, Jiang G, Koivisto L, Wienke D, Isacke C, Larjava H, et al. Expression of Endo180 is spatially and temporally regulated during wound healing. Histopathology. 2006;49:634-48 pubmed
    ..The findings suggest that Endo180 plays a role in re-epithelialization and connective tissue remodelling during wound regeneration. ..