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F Berditchevski, MM Zutter and ME Hemler
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Here we identified several new integrin/TM4 protein complexes on the cell surface. By immunoprecipitation using nonstringent conditions, and by reciprocal immunoprecipitation, we found that alpha 3 beta 1 and alpha 6 beta 1 integrins but not alpha 2 beta 1, alpha 5 beta 1, or alpha 6 beta 4 integrins associated with CD9 and CD81 in alpha 3 beta 1/CD81, alpha 3 beta 1/CD9, alpha 6 beta 1/CD81, and alpha 6 beta 1/CD9 complexes. Also, cross-linking experiments established that alpha 3 beta 1/CD81, alpha 3 beta 1/CD9, and alpha 3 beta 1/CD63 associations occur on the surface of intact cells and suggested that a critical interaction site is located within extracellular domains. Cross-linking in conjunction with reimmunoprecipitation indicated that larger multi- component alpha 3 beta 1/TM4/TM4 complexes (alpha 3 beta 1/CD9/CD63, alpha 3 beta 1/CD81/CD63, and alpha 3 beta 1/CD9/CD81) also could be detected on the cell surface. Immunofluorescent staining showed redistribution of alpha 3 beta 1/TM4 complexes toward the periphery of cells plated on various extracellular matrix substrates and also showed that these complexes were localized in cell footprints. Staining of human tissues yielded additional results consistent with co- localization of alpha 3 beta 1 and CD9, CD63, and CD81 proteins. In conclusion we suggest that the prevalence of integrin/TM4 complexes in diverse cellular environments is indicative of their general physiological importance.
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I. Tachibana, J. Bodorova, F. Berditchevski, M. M. Zutter, and M. E. Hemler NAG-2, a Novel Transmembrane-4 Superfamily (TM4SF) Protein That Complexes with Integrins and Other TM4SF Proteins J. Biol. Chem., November 14, 1997; 272(46): 29181 - 29189. [Abstract] [Full Text] [PDF]
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S. Z. Domanico, A. J. Pelletier, W. L. Havran, and V. Quaranta Integrin alpha 6Abeta 1 Induces CD81-dependent Cell Motility without Engaging the Extracellular Matrix Migration Substrate Mol. Biol. Cell, November 1, 1997; 8(11): 2253 - 2265. [Abstract] [Full Text]
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M. A. Abitorabi, R. K. Pachynski, R. E. Ferrando, M. Tidswell, and D. J. Erle Presentation of Integrins on Leukocyte Microvilli: A Role for the Extracellular Domain in Determining Membrane Localization J. Cell Biol., October 20, 1997; 139(2): 563 - 571. [Abstract] [Full Text] [PDF]
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E. N. Tsitsikov, J. C. Gutierrez-Ramos, and R. S. Geha Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice PNAS, September 30, 1997; 94(20): 10844 - 10849. [Abstract] [Full Text] [PDF]
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S. A. Banerjee, M. Hadjiargyrou, and P. H. Patterson An Antibody to the Tetraspan Membrane Protein CD9 Promotes Neurite Formation in a Partially alpha 3beta 1 Integrin-Dependent Manner J. Neurosci., April 15, 1997; 17(8): 2756 - 2765. [Abstract] [Full Text] [PDF]
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P. D. Tahiliani, L. Singh, K. L. Auer, and S. E. LaFlamme The Role of Conserved Amino Acid Motifs within the Integrin beta 3 Cytoplasmic Domain in Triggering Focal Adhesion Kinase Phosphorylation J. Biol. Chem., March 21, 1997; 272(12): 7892 - 7898. [Abstract] [Full Text] [PDF]
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F. Berditchevski, K. F. Tolias, K. Wong, C. L. Carpenter, and M. E. Hemler A Novel Link between Integrins, Transmembrane-4 Superfamily Proteins (CD63 and CD81), and Phosphatidylinositol 4-Kinase J. Biol. Chem., January 31, 1997; 272(5): 2595 - 2598. [Abstract] [Full Text] [PDF]
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P. M. Sincock, G. Mayrhofer, and L. K. Ashman Localization of the Transmembrane 4 Superfamily (TM4SF) Member PETA-3 (CD151) in Normal Human Tissues: Comparison with CD9, CD63, and {alpha}5ss1 Integrin J. Histochem. Cytochem., January 1, 1997; 45(4): 515 - 526. [Abstract] [Full Text] [PDF]
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P. J. Keely and L. V. Parise The alpha 2beta 1 Integrin Is a Necessary Co-receptor for Collagen-induced Activation of Syk and the Subsequent Phosphorylation of Phospholipase Cgamma 2 in Platelets J. Biol. Chem., October 25, 1996; 271(43): 26668 - 26676. [Abstract] [Full Text] [PDF]
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R. F. Thorne, J. F. Marshall, D. R. Shafren, P. G. Gibson, I. R. Hart, and G. F. Burns The Integrins alpha 3beta 1 and alpha 6beta 1 Physically and Functionally Associate with CD36 in Human Melanoma Cells. REQUIREMENT FOR THE EXTRACELLULAR DOMAIN OF CD36 J. Biol. Chem., November 3, 2000; 275(45): 35264 - 35275. [Abstract] [Full Text] [PDF]
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C. Claas, C. S. Stipp, and M. E. Hemler Evaluation of Prototype Transmembrane 4 Superfamily Protein Complexes and Their Relation to Lipid Rafts J. Biol. Chem., March 9, 2001; 276(11): 7974 - 7984. [Abstract] [Full Text] [PDF]
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C. S. Stipp, D. Orlicky, and M. E. Hemler FPRP, a Major, Highly Stoichiometric, Highly Specific CD81- and CD9-associated Protein J. Biol. Chem., February 9, 2001; 276(7): 4853 - 4862. [Abstract] [Full Text] [PDF]
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S. Charrin, F. Le Naour, M. Oualid, M. Billard, G. Faure, S. M. Hanash, C. Boucheix, and E. Rubinstein The Major CD9 and CD81 Molecular Partner. IDENTIFICATION AND CHARACTERIZATION OF THE COMPLEXES J. Biol. Chem., April 20, 2001; 276(17): 14329 - 14337. [Abstract] [Full Text] [PDF]
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X. A. Zhang, A. L. Bontrager, and M. E. Hemler Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific beta 1 Integrins J. Biol. Chem., June 29, 2001; 276(27): 25005 - 25013. [Abstract] [Full Text] [PDF]
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T. L. Davis, I. Rabinovitz, B. W. Futscher, M. Schnolzer, F. Burger, Y. Liu, M. Kulesz-Martin, and A. E. Cress Identification of a Novel Structural Variant of the alpha 6 Integrin J. Biol. Chem., July 6, 2001; 276(28): 26099 - 26106. [Abstract] [Full Text] [PDF]
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F. Berditchevski, E. Gilbert, M. R. Griffiths, S. Fitter, L. Ashman, and S. J. Jenner Analysis of the CD151{middle dot}alpha 3beta 1 Integrin and CD151{middle dot}Tetraspanin Interactions by Mutagenesis J. Biol. Chem., October 26, 2001; 276(44): 41165 - 41174. [Abstract] [Full Text] [PDF]
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J. Hernandez-Torres, M. Yunta, and P. A. Lazo Differential Cooperation between Regulatory Sequences Required for Human CD53 Gene Expression J. Biol. Chem., September 14, 2001; 276(38): 35405 - 35413. [Abstract] [Full Text] [PDF]
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C. S. Stipp, T. V. Kolesnikova, and M. E. Hemler EWI-2 Is a Major CD9 and CD81 Partner and Member of a Novel Ig Protein Subfamily J. Biol. Chem., October 26, 2001; 276(44): 40545 - 40554. [Abstract] [Full Text] [PDF]
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K. Nakamura, T. Mitamura, T. Takahashi, T. Kobayashi, and E. Mekada Importance of the Major Extracellular Domain of CD9 and the Epidermal Growth Factor (EGF)-like Domain of Heparin-binding EGF-like Growth Factor for Up-regulation of Binding and Activity J. Biol. Chem., June 9, 2000; 275(24): 18284 - 18290. [Abstract] [Full Text] [PDF]
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A. Woods and J. R. Couchman Integrin Modulation by Lateral Association J. Biol. Chem., August 4, 2000; 275(32): 24233 - 24236. [Full Text] [PDF]
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M. Oka, K. Tagoku, T. L. Russell, Y. Nakano, T. Hamazaki, E. M. Meyer, T. Yokota, and N. Terada CD9 Is Associated with Leukemia Inhibitory Factor-mediated Maintenance of Embryonic Stem Cells Mol. Biol. Cell, April 1, 2002; 13(4): 1274 - 1281. [Abstract] [Full Text] [PDF]
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