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. 2000 Nov 1;351(Pt 3):629–637.

Specific interactions among transmembrane 4 superfamily (TM4SF) proteins and phosphoinositide 4-kinase.

R L Yauch 1, M E Hemler 1
PMCID: PMC1221402  PMID: 11042117

Abstract

In earlier work we established that phosphoinositide 4-kinase (PI 4-kinase) may associate with transmembrane 4 superfamily (TM4SF, tetraspanin) proteins, but critical specificity issues were not addressed. Here we demonstrate that at least five different TM4SF proteins (CD9, CD63, CD81, CD151 and A15/TALLA1) can associate with a similar or identical 55 kDa type II PI 4-kinase. These associations were specific, since we found no evidence for other phosphoinositide kinases (e.g. phosphoinositide 3-kinase and phosphoinositide-4-phosphate 5-kinase) associating with TM4SF proteins, and many other TM4SF proteins (including CD82 and CD53) did not associate with PI 4-kinase. CD63-PI 4-kinase complexes were almost entirely intracellular, and thus are distinct from other TM4SF-PI 4-kinase complexes (e.g. involving CD9), which are largely located in the plasma membrane. These results suggest that a specific subset of TM4SF proteins may recruit PI 4-kinase to specific membrane locations, and thereby influence phosphoinositide-dependent signalling.

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Selected References

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  1. Anton E. S., Hadjiargyrou M., Patterson P. H., Matthew W. D. CD9 plays a role in Schwann cell migration in vitro. J Neurosci. 1995 Jan;15(1 Pt 2):584–595. doi: 10.1523/JNEUROSCI.15-01-00584.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balla T., Downing G. J., Jaffe H., Kim S., Zólyomi A., Catt K. J. Isolation and molecular cloning of wortmannin-sensitive bovine type III phosphatidylinositol 4-kinases. J Biol Chem. 1997 Jul 18;272(29):18358–18366. doi: 10.1074/jbc.272.29.18358. [DOI] [PubMed] [Google Scholar]
  3. Berditchevski F., Bazzoni G., Hemler M. E. Specific association of CD63 with the VLA-3 and VLA-6 integrins. J Biol Chem. 1995 Jul 28;270(30):17784–17790. doi: 10.1074/jbc.270.30.17784. [DOI] [PubMed] [Google Scholar]
  4. Berditchevski F., Tolias K. F., Wong K., Carpenter C. L., Hemler M. E. A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J Biol Chem. 1997 Jan 31;272(5):2595–2598. doi: 10.1074/jbc.272.5.2595. [DOI] [PubMed] [Google Scholar]
  5. Berditchevski F., Zutter M. M., Hemler M. E. Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins). Mol Biol Cell. 1996 Feb;7(2):193–207. doi: 10.1091/mbc.7.2.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bergelson J. M., St John N. F., Kawaguchi S., Pasqualini R., Berdichevsky F., Hemler M. E., Finberg R. W. The I domain is essential for echovirus 1 interaction with VLA-2. Cell Adhes Commun. 1994 Oct;2(5):455–464. doi: 10.3109/15419069409004455. [DOI] [PubMed] [Google Scholar]
  7. Berger G., Massé J. M., Cramer E. M. Alpha-granule membrane mirrors the platelet plasma membrane and contains the glycoproteins Ib, IX, and V. Blood. 1996 Feb 15;87(4):1385–1395. [PubMed] [Google Scholar]
  8. Campbell C. R., Fishman J. B., Fine R. E. Coated vesicles contain a phosphatidylinositol kinase. J Biol Chem. 1985 Sep 15;260(20):10948–10951. [PubMed] [Google Scholar]
  9. Chan B. M., Hemler M. E. Multiple functional forms of the integrin VLA-2 can be derived from a single alpha 2 cDNA clone: interconversion of forms induced by an anti-beta 1 antibody. J Cell Biol. 1993 Jan;120(2):537–543. doi: 10.1083/jcb.120.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cramer E. M., Berger G., Berndt M. C. Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1. Blood. 1994 Sep 15;84(6):1722–1730. [PubMed] [Google Scholar]
  11. Domanico S. Z., Pelletier A. J., Havran W. L., Quaranta V. Integrin alpha 6A beta 1 induces CD81-dependent cell motility without engaging the extracellular matrix migration substrate. Mol Biol Cell. 1997 Nov;8(11):2253–2265. doi: 10.1091/mbc.8.11.2253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Endemann G. C., Graziani A., Cantley L. C. A monoclonal antibody distinguishes two types of phosphatidylinositol 4-kinase. Biochem J. 1991 Jan 1;273(Pt 1):63–66. doi: 10.1042/bj2730063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Endemann G., Dunn S. N., Cantley L. C. Bovine brain contains two types of phosphatidylinositol kinase. Biochemistry. 1987 Oct 20;26(21):6845–6852. doi: 10.1021/bi00395a039. [DOI] [PubMed] [Google Scholar]
  14. Escola J. M., Kleijmeer M. J., Stoorvogel W., Griffith J. M., Yoshie O., Geuze H. J. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 1998 Aug 7;273(32):20121–20127. doi: 10.1074/jbc.273.32.20121. [DOI] [PubMed] [Google Scholar]
  15. Fruman D. A., Meyers R. E., Cantley L. C. Phosphoinositide kinases. Annu Rev Biochem. 1998;67:481–507. doi: 10.1146/annurev.biochem.67.1.481. [DOI] [PubMed] [Google Scholar]
  16. Fukudome K., Furuse M., Imai T., Nishimura M., Takagi S., Hinuma Y., Yoshie O. Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation: altered glycosylation of C33 antigen in HTLV-1-positive T cells. J Virol. 1992 Mar;66(3):1394–1401. doi: 10.1128/jvi.66.3.1394-1401.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Graziani A., Ling L. E., Endemann G., Carpenter C. L., Cantley L. C. Purification and characterization of human erythrocyte phosphatidylinositol 4-kinase. Phosphatidylinositol 4-kinase and phosphatidylinositol 3-monophosphate 4-kinase are distinct enzymes. Biochem J. 1992 May 15;284(Pt 1):39–45. doi: 10.1042/bj2840039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hammond C., Denzin L. K., Pan M., Griffith J. M., Geuze H. J., Cresswell P. The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules. J Immunol. 1998 Oct 1;161(7):3282–3291. [PubMed] [Google Scholar]
  19. Hemler M. E., Huang C., Takada Y., Schwarz L., Strominger J. L., Clabby M. L. Characterization of the cell surface heterodimer VLA-4 and related peptides. J Biol Chem. 1987 Aug 25;262(24):11478–11485. [PubMed] [Google Scholar]
  20. Hemler M. E. Integrin associated proteins. Curr Opin Cell Biol. 1998 Oct;10(5):578–585. doi: 10.1016/s0955-0674(98)80032-x. [DOI] [PubMed] [Google Scholar]
  21. Hemler M. E., Mannion B. A., Berditchevski F. Association of TM4SF proteins with integrins: relevance to cancer. Biochim Biophys Acta. 1996 Jun 7;1287(2-3):67–71. doi: 10.1016/0304-419x(96)00007-8. [DOI] [PubMed] [Google Scholar]
  22. Hemler M. E., Sanchez-Madrid F., Flotte T. J., Krensky A. M., Burakoff S. J., Bhan A. K., Springer T. A., Strominger J. L. Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines. J Immunol. 1984 Jun;132(6):3011–3018. [PubMed] [Google Scholar]
  23. Hemler M. E., Strominger J. L. Monoclonal antibodies reacting with immunogenic mycoplasma proteins present in human hematopoietic cell lines. J Immunol. 1982 Dec;129(6):2734–2738. [PubMed] [Google Scholar]
  24. Hirano T., Higuchi T., Ueda M., Inoue T., Kataoka N., Maeda M., Fujiwara H., Fujii S. CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5. Mol Hum Reprod. 1999 Feb;5(2):162–167. doi: 10.1093/molehr/5.2.162. [DOI] [PubMed] [Google Scholar]
  25. Jones P. H., Bishop L. A., Watt F. M. Functional significance of CD9 association with beta 1 integrins in human epidermal keratinocytes. Cell Adhes Commun. 1996 Nov;4(4-5):297–305. doi: 10.3109/15419069609010773. [DOI] [PubMed] [Google Scholar]
  26. Kristiansen S., Ramlal T., Klip A. Phosphatidylinositol 4-kinase, but not phosphatidylinositol 3-kinase, is present in GLUT4-containing vesicles isolated from rat skeletal muscle. Biochem J. 1998 Oct 15;335(Pt 2):351–356. doi: 10.1042/bj3350351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Le Naour F., Rubinstein E., Jasmin C., Prenant M., Boucheix C. Severely reduced female fertility in CD9-deficient mice. Science. 2000 Jan 14;287(5451):319–321. doi: 10.1126/science.287.5451.319. [DOI] [PubMed] [Google Scholar]
  28. Lemke H., Hammerling G. J., Hohmann C., Rajewsky K. Hybrid cell lines secreting monoclonal antibody specific for major histocompatibility antigens of the mouse. Nature. 1978 Jan 19;271(5642):249–251. doi: 10.1038/271249a0. [DOI] [PubMed] [Google Scholar]
  29. Ling L. E., Schulz J. T., Cantley L. C. Characterization and purification of membrane-associated phosphatidylinositol-4-phosphate kinase from human red blood cells. J Biol Chem. 1989 Mar 25;264(9):5080–5088. [PubMed] [Google Scholar]
  30. Maecker H. T., Todd S. C., Levy S. The tetraspanin superfamily: molecular facilitators. FASEB J. 1997 May;11(6):428–442. [PubMed] [Google Scholar]
  31. Mannion B. A., Berditchevski F., Kraeft S. K., Chen L. B., Hemler M. E. Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). J Immunol. 1996 Sep 1;157(5):2039–2047. [PubMed] [Google Scholar]
  32. Metzelaar M. J., Wijngaard P. L., Peters P. J., Sixma J. J., Nieuwenhuis H. K., Clevers H. C. CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells. J Biol Chem. 1991 Feb 15;266(5):3239–3245. [PubMed] [Google Scholar]
  33. Miyado K., Yamada G., Yamada S., Hasuwa H., Nakamura Y., Ryu F., Suzuki K., Kosai K., Inoue K., Ogura A. Requirement of CD9 on the egg plasma membrane for fertilization. Science. 2000 Jan 14;287(5451):321–324. doi: 10.1126/science.287.5451.321. [DOI] [PubMed] [Google Scholar]
  34. Miyake M., Koyama M., Seno M., Ikeyama S. Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody M31-15, which inhibits cell motility. J Exp Med. 1991 Dec 1;174(6):1347–1354. doi: 10.1084/jem.174.6.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nakamura K., Iwamoto R., Mekada E. Membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) and diphtheria toxin receptor-associated protein (DRAP27)/CD9 form a complex with integrin alpha 3 beta 1 at cell-cell contact sites. J Cell Biol. 1995 Jun;129(6):1691–1705. doi: 10.1083/jcb.129.6.1691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nichols T. C., Guthridge J. M., Karp D. R., Molina H., Fletcher D. R., Holers V. M. Gamma-glutamyl transpeptidase, an ecto-enzyme regulator of intracellular redox potential, is a component of TM4 signal transduction complexes. Eur J Immunol. 1998 Dec;28(12):4123–4129. doi: 10.1002/(SICI)1521-4141(199812)28:12<4123::AID-IMMU4123>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
  37. Nishibori M., Cham B., McNicol A., Shalev A., Jain N., Gerrard J. M. The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin. J Clin Invest. 1993 Apr;91(4):1775–1782. doi: 10.1172/JCI116388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Nishikawa K., Toker A., Wong K., Marignani P. A., Johannes F. J., Cantley L. C. Association of protein kinase Cmu with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem. 1998 Sep 4;273(36):23126–23133. doi: 10.1074/jbc.273.36.23126. [DOI] [PubMed] [Google Scholar]
  39. Peters P. J., Borst J., Oorschot V., Fukuda M., Krähenbühl O., Tschopp J., Slot J. W., Geuze H. J. Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med. 1991 May 1;173(5):1099–1109. doi: 10.1084/jem.173.5.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pike L. J., Miller J. M. Cholesterol depletion delocalizes phosphatidylinositol bisphosphate and inhibits hormone-stimulated phosphatidylinositol turnover. J Biol Chem. 1998 Aug 28;273(35):22298–22304. doi: 10.1074/jbc.273.35.22298. [DOI] [PubMed] [Google Scholar]
  41. Prasad K. V., Kapeller R., Janssen O., Repke H., Duke-Cohan J. S., Cantley L. C., Rudd C. E. Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI 4-kinase. Mol Cell Biol. 1993 Dec;13(12):7708–7717. doi: 10.1128/mcb.13.12.7708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Radford K. J., Thorne R. F., Hersey P. Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line. J Immunol. 1997 Apr 1;158(7):3353–3358. [PubMed] [Google Scholar]
  43. Rubinstein E., Poindessous-Jazat V., Le Naour F., Billard M., Boucheix C. CD9, but not other tetraspans, associates with the beta1 integrin precursor. Eur J Immunol. 1997 Aug;27(8):1919–1927. doi: 10.1002/eji.1830270815. [DOI] [PubMed] [Google Scholar]
  44. Schwartz-Albiez R., Dörken B., Hofmann W., Moldenhauer G. The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein. J Immunol. 1988 Feb 1;140(3):905–914. [PubMed] [Google Scholar]
  45. Serru V., Le Naour F., Billard M., Azorsa D. O., Lanza F., Boucheix C., Rubinstein E. Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions. Biochem J. 1999 May 15;340(Pt 1):103–111. [PMC free article] [PubMed] [Google Scholar]
  46. Shaw A. R., Domanska A., Mak A., Gilchrist A., Dobler K., Visser L., Poppema S., Fliegel L., Letarte M., Willett B. J. Ectopic expression of human and feline CD9 in a human B cell line confers beta 1 integrin-dependent motility on fibronectin and laminin substrates and enhanced tyrosine phosphorylation. J Biol Chem. 1995 Oct 13;270(41):24092–24099. doi: 10.1074/jbc.270.41.24092. [DOI] [PubMed] [Google Scholar]
  47. Sincock P. M., Fitter S., Parton R. G., Berndt M. C., Gamble J. R., Ashman L. K. PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function. J Cell Sci. 1999 Mar;112(Pt 6):833–844. doi: 10.1242/jcs.112.6.833. [DOI] [PubMed] [Google Scholar]
  48. Sugiura T., Berditchevski F. Function of alpha3beta1-tetraspanin protein complexes in tumor cell invasion. Evidence for the role of the complexes in production of matrix metalloproteinase 2 (MMP-2). J Cell Biol. 1999 Sep 20;146(6):1375–1389. doi: 10.1083/jcb.146.6.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Tachibana I., Bodorova J., Berditchevski F., Zutter M. M., Hemler M. E. NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins. J Biol Chem. 1997 Nov 14;272(46):29181–29189. doi: 10.1074/jbc.272.46.29181. [DOI] [PubMed] [Google Scholar]
  50. Takagi S., Fujikawa K., Imai T., Fukuhara N., Fukudome K., Minegishi M., Tsuchiya S., Konno T., Hinuma Y., Yoshie O. Identification of a highly specific surface marker of T-cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily. Int J Cancer. 1995 May 29;61(5):706–715. doi: 10.1002/ijc.2910610519. [DOI] [PubMed] [Google Scholar]
  51. Todd S. C., Doctor V. S., Levy S. Sequences and expression of six new members of the tetraspanin/TM4SF family. Biochim Biophys Acta. 1998 Jul 30;1399(1):101–104. doi: 10.1016/s0167-4781(98)00087-6. [DOI] [PubMed] [Google Scholar]
  52. Vischer U. M., Wagner D. D. CD63 is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1993 Aug 15;82(4):1184–1191. [PubMed] [Google Scholar]
  53. Walker D. H., Dougherty N., Pike L. J. Purification and characterization of a phosphatidylinositol kinase from A431 cells. Biochemistry. 1988 Aug 23;27(17):6504–6511. doi: 10.1021/bi00417a046. [DOI] [PubMed] [Google Scholar]
  54. Waugh M. G., Lawson D., Tan S. K., Hsuan J. J. Phosphatidylinositol 4-phosphate synthesis in immunoisolated caveolae-like vesicles and low buoyant density non-caveolar membranes. J Biol Chem. 1998 Jul 3;273(27):17115–17121. doi: 10.1074/jbc.273.27.17115. [DOI] [PubMed] [Google Scholar]
  55. Wiedemann C., Schäfer T., Burger M. M. Chromaffin granule-associated phosphatidylinositol 4-kinase activity is required for stimulated secretion. EMBO J. 1996 May 1;15(9):2094–2101. [PMC free article] [PubMed] [Google Scholar]
  56. Wiedemann C., Schäfer T., Burger M. M., Sihra T. S. An essential role for a small synaptic vesicle-associated phosphatidylinositol 4-kinase in neurotransmitter release. J Neurosci. 1998 Aug 1;18(15):5594–5602. doi: 10.1523/JNEUROSCI.18-15-05594.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wong K., Meyers ddR, Cantley L. C. Subcellular locations of phosphatidylinositol 4-kinase isoforms. J Biol Chem. 1997 May 16;272(20):13236–13241. doi: 10.1074/jbc.272.20.13236. [DOI] [PubMed] [Google Scholar]
  58. Wright M. D., Tomlinson M. G. The ins and outs of the transmembrane 4 superfamily. Immunol Today. 1994 Dec;15(12):588–594. doi: 10.1016/0167-5699(94)90222-4. [DOI] [PubMed] [Google Scholar]
  59. Yauch R. L., Berditchevski F., Harler M. B., Reichner J., Hemler M. E. Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Mol Biol Cell. 1998 Oct;9(10):2751–2765. doi: 10.1091/mbc.9.10.2751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Yauch R. L., Kazarov A. R., Desai B., Lee R. T., Hemler M. E. Direct extracellular contact between integrin alpha(3)beta(1) and TM4SF protein CD151. J Biol Chem. 2000 Mar 31;275(13):9230–9238. doi: 10.1074/jbc.275.13.9230. [DOI] [PubMed] [Google Scholar]
  61. Yelton D. E., Desaymard C., Scharff M. D. Use of monoclonal anti-mouse immunoglobulin to detect mouse antibodies. Hybridoma. 1981;1(1):5–11. doi: 10.1089/hyb.1.1981.1.5. [DOI] [PubMed] [Google Scholar]
  62. Yáez-Mó M., Alfranca A., Cabañas C., Marazuela M., Tejedor R., Ursa M. A., Ashman L. K., de Landázuri M. O., Sánchez-Madrid F. Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions. J Cell Biol. 1998 May 4;141(3):791–804. doi: 10.1083/jcb.141.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Zent R., Fenczik C. A., Calderwood D. A., Liu S., Dellos M., Ginsberg M. H. Class- and splice variant-specific association of CD98 with integrin beta cytoplasmic domains. J Biol Chem. 2000 Feb 18;275(7):5059–5064. doi: 10.1074/jbc.275.7.5059. [DOI] [PubMed] [Google Scholar]

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