A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase.
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.
Berditchevski
F
F
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tolias
K F
KF
Wong
K
K
Carpenter
C L
CL
Hemler
M E
ME
D019870:1-Phosphatidylinositol 4-Kinase; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D005354:Fibrosarcoma; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000302:isolation & purification / Q000378:metabolism; D008565:Membrane Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000302:isolation & purification / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554586:CD63 protein, human; C554798:CD81 protein, human; D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; D016023:Integrins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase