A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase

J Biol Chem. 1997 Jan 31;272(5):2595-8. doi: 10.1074/jbc.272.5.2595.


Enzymatic and immunochemical assays show a phosphatidylinositol 4-kinase in novel and specific complexes with proteins (CD63 and CD81) of the transmembrane 4 superfamily (TM4SF) and an integrin (alpha3beta1). The size (55 kDa) and other properties of the phosphatidylinositol 4-kinase (PI 4-K) (stimulated by nonionic detergent, inhibited by adenosine, inhibited by monoclonal antibody 4CG5) are consistent with PI 4-K type II. Not only was PI 4-K associated with alpha3beta1-CD63 complexes in alpha3-transfected K562 cells, but also it could be co-purified from CD63 in untransfected K562 cells lacking alpha3beta1. Thus, TM4SF proteins may link PI 4-K activity to the alpha3beta1 integrin. The alpha5beta1 integrin, which does not associate with TM4SF proteins, was not associated with PI 4-K. Notably, alpha3beta1-CD63-CD81-PI 4-K complexes are located in focal complexes at the cell periphery rather than in focal adhesions. The novel linkage between integrins, transmembrane 4 proteins, and phosphoinositide signaling at the cell periphery may play a key role in cell motility and provides a signaling pathway distinct from conventional integrin signaling through focal adhesion kinase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase
  • Antibodies, Monoclonal
  • Antigens, CD / analysis*
  • Antigens, CD / isolation & purification
  • Antigens, CD / metabolism*
  • Cell Adhesion Molecules / isolation & purification
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Fibrosarcoma
  • Humans
  • Integrin alpha3beta1
  • Integrins / isolation & purification
  • Integrins / metabolism
  • Membrane Proteins*
  • Phosphotransferases (Alcohol Group Acceptor) / isolation & purification
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Platelet Membrane Glycoproteins / isolation & purification
  • Platelet Membrane Glycoproteins / metabolism*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Tetraspanin 28
  • Tetraspanin 30
  • Transfection
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Antigens, CD
  • CD63 protein, human
  • CD81 protein, human
  • Cell Adhesion Molecules
  • Integrin alpha3beta1
  • Integrins
  • Membrane Proteins
  • Platelet Membrane Glycoproteins
  • Recombinant Proteins
  • Tetraspanin 28
  • Tetraspanin 30
  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-Phosphatidylinositol 4-Kinase