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PROW: CD40
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PROW and IWHLDA present the GUIDE on:
CD40
Authors: John Gordon; Anita Challa; John Pound
Reviewer: Randolph J. Noelle
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OVERVIEW
MOLECULAR FAMILIES  
  • Families in which CD40 is a member

    ALTERNATE NAMES  

  • Bp50

    MAJOR LINKS  

  • NCBI LocusLink Record: 958
  • Mendelian Inheritance in Man (OMIM): 109535
  • SwissProt annotated protein record: P25942
  • AUTHOR'S ADDITIONAL INSIGHTS  

  • Intriguing question of different epitopes displaying differential functions. Is there another ligand(s)?
  • Signal transduction pathways engaged appear different at different stages of B cell differentiation
  • Plays a central role in the regulation of cell-mediated immunity as well as antibody mediated immunity**
    SYSTEM VIEW
    DISEASE RELEVANCE / FUNCTION IN INTACT  
  • Central to T cell dependent (TD)-responses
  • May influence survival of B cell lymphomas
  • May be an important target for the control of graft rejection, T and antibody mediated autoimmune diseases**

    CELLULAR FUNCTION  

  • On B cells, involved in growth, differentiation, and isotype-switching
  • Potent rescue signal from apoptosis in germinal center B cells
  • Promotes cytokine production in macrophages and dendritic cells
  • Up-regulates adhesion molecules on dendritic cells and keratinocytes
  • Stimulates growth arrest in epithelial cells

    CELLULAR EXPRESSION  

  • B cells including pro-B through to plasma cells (although weak on latter)
  • Basal epithelial cells plus epithelial cell carcinomas
  • Macrophages
  • Follicular dendritic cells
  • Endothelial cells
  • Fibroblasts
  • Keratinocytes
  • Interdigitating cells
  • CD34+ hemopoietic cell progenitors also positive
    GENE
    TRANSCRIPTION REGULATING MOLECULES  
    - No information


    TRANSCRIPT
    POST-TRANSCRIPTIONAL MODIFICATION  
  • No evidence of differentially spliced products
    PROTEIN
    BIOCHEMICAL ACTIVITY  
    - No information

    PROTEIN SEQUENCE LINKS  

  • SwissProt annotated protein record: P25942
  • PROTEIN SEQUENCE ANNOTATION  

  • Single chain type I transmembrane molecule
  • Cysteine-rich extracellular domain of 193 amino acids, a transmembrane region of 22 hydrophobic residues, and a cytoplasmic region of 42 amino acids
  • Cytoplasmic region appears to contain two distinct functional domains (Goldstein and Watts 1996)

    PROTEIN PHYSICAL PROPERTIES  

    CELL TYPEMW UNREDUCEDMW REDUCEDComment
    B lymphocytes (85 kDa dimers) 48 kDa  

    POST-TRANSLATIONAL MODIFICATION  

  • Glycosylated: 48 kDa glycoprotein appearing as 39 kDa post-deglycosylation
  • Phosphorylated on serine/threonine residues. No tyrosine phosphorylation
    MOLECULAR INTERACTIONS
    SUBSTRATES  
    - No information

    ENZYME FOR WHICH THIS IS A SUBSTRATE  
    - No information

    OTHER LIGANDS AND ASSOCIATED MOLECULES  

    MOLECULECOMMENT
    CD40L Inducible member of TNF-family of molecules on TH cells

    REFERENCES
    REVIEWS  
    1. Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, Van Kooten C, Liu YJ, Rousset F and Saeland S. 1994. The CD40 antigen and its ligand. Annu Rev Immunol 12:881-922 PubMed
    2. Foy TM, Aruffo A, Bajorath J, Buhlmann JE and Noelle RJ. 1996. Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 14:591-617 PubMed
    3. Gordon J. 1995. CD40 and its ligand: central players in B lymphocyte survival, growth, and differentiation. Blood Rev 9:53-56 PubMed
    4. Gordon J, Katira A, Holder M, MacDonald I and Pound J. 1994. Central role of CD40 and its ligand in B lymphocyte responses to T-dependent antigens. Cell Mol Biol (Noisy-le-grand) 40:1-13 PubMed

    PRIMARY CITATIONS  
    5. Clark EA and Ledbetter JA. 1986. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A 83:4494-4498 PubMed
    6. Goldstein MD and Watts TH. 1996. Identification of distinct domains in CD40 involved in B7-1 induction or growth inhibition. J Immunol 157:2837-2843 PubMed
    7. Paulie S, Ehlin-Henriksson B, Mellstedt H, Koho H, Ben-Aissa H and Perlmann P. 1985. A p50 surface antigen restricted to human urinary bladder carcinomas and B lymphocytes. Cancer Immunol Immunother 20:23-28 PubMed

    WWW RESOURCES  


    * indicates amended by reviewer, ** indicates added by reviewer
    Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission
    Modified 12/01/99   mpr@mail.nih.gov