ORIGINAL INVESTIGATION

Medical Microbiology and Immunology

, Volume 186, Issue 2, pp 115-123

First online:

Protein tyrosine kinase activation provides an early and obligatory signal in anti-FRP-1/CD98/4F2 monoclonal antibody induced cell fusion mediated by HIV gp160

  • Nobutada TabataAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
  • , Masaru IdoAffiliated withDepartment of Molecular Pathobiology, Mie University School of Medicine, Mie Prefecture, Japan
  • , Shigeru SugaAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
  • , Shinji OhgimotoAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
  • , Masato TsurudomeAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
  • , Mitsuo KawanoAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
  • , Machiko NishioAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
  • , Noriko WatanabeAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
  • , Kousuke OkamotoAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
    • , Hiroshi KomadaAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp
    • , Minoru SakuraiAffiliated withDepartment of Pediatrics, Mie University, School of Medicine, Mie Prefecture, Japan
    • , Y. ItoAffiliated withDepartment of Microbiology, Mie University School of Medicine 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514 Japan, Tel. & Fax: 81-592-31-5008; e-mail: ito@doc.medic.mie-u.ac.jp

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

The mechanism by which anti-fusion regulatory protein-1 (FRP-1) monoclonal antibody (mAb) induced cell fusion was investigated using U2ME-7 cells that are CD4+U937 cells transfected with the HIV gp160 gene. Protein kinase inhibitors (H-7, H-89, herbimycin A and genistein) suppressed cell fusion of Cd+U2ME-7 cells induced by anti-FRP-1 mAb. H-7 and H-89 also inhibited the cell aggregation, but herbimycin A and genistein did not. Intriguingly, only when herbimycin A was added either before or simultaneously with addition of anti-FRP-1 mAb, was cell fusion suppressed, suggesting that tyrosine kinase is related with the initial step of polykaryocyte formation. Anti-FRP-1 mAb induced the rapid tyrosine phosphorylation of multiple cellular proteins. These effects occurred within 1 min and returned to near baseline by 60 min. The rapid tyrosine phosphorylation was suppressed by herbimycin A and genistein. Although it remains to be determined which protein tyrosine kinase(s) is involved in this response, pp130 tyrosine phosphorylation appears to be a specific and early signal transmitted after the interaction of FRP-1 with a specific antibody. pp130 was present in the cytosol fraction and was distinct from pp125FAK, p130CAS, vinculin, and β1-integrin. Thus, our study may present evidence for a novel pathway of protein tyrosine kinases that phosphorylate specific, still unknown protein substrates during polykaryocyte formation.

Key words Fusion regulatory protein-1 CD98 Cell fusion Signal transduction Tyrosine kinase