Characterization of the cell surface heterodimer VLA-4 and related peptides

M. E. Hemler, C. Huang, Yoshikazu Takada, L. Schwarz, J. L. Strominger, M. L. Clabby

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Abstract

A monoclonal antibody (B-5G10) was produced which specifically recognizes the M(r) 150,000/130,000 VLA-4 complex on the surface of human cells. Crosslinking studies indicated that the M(r) 150,000 α4 subunit of VLA-4 is in noncovalent 1:1 associated with the M(r) 130,000 VLA β subunit. In the absence of crosslinking, the VLA-4 α4β subunit complex was easily dissociated, especially in Nonidet P-40 detergent, or at elevated pH (above 8.0). Studies of dissociated subunits showed that B-5G10 recognize an epitope on the M(r) 150,000 α4 subunit of VLA-4, whereas the β subunit is immunologically identical to the M(r) 130,000 β subunit common to all VLA heterodimes. VLA-4 is widely distributed on hematopoietic cells, including thymocytes, peripheral blood lymphocytes, monocytes, activated T cells, T and B lymphoblastoid cell lines, and myeloid cell lines. However, VLA-4 is only weakly expressed on most adherent cell lines tested. Immunoprecipitates of VLA-4 often contain additional proteins of M(r) 80,000 and M(r) 70,000. These are probably derived from the M(r) 150,000 α4 subunit because: 1) they are both recognized by anti-α4 sera, but not anti-β sera; 2) the sum of their sizes is equal to the size of α4; 3) they are selectively coexpressed with α4 and not other VLA α subunits; 4) the M(r) 80,000 protein has an identical NH2-terminal sequence to α4; 5) like α4, the M(r) 70,000 and 80,000 peptides can variably associate with the VLA β subunits; and 6) trypsin appears to cleave the M(r) 150,000 α4 subunit into products of M(r) 70,000 and 80,000.

Original languageEnglish (US)
Pages (from-to)11478-11485
Number of pages8
JournalJournal of Biological Chemistry
Volume262
Issue number24
StatePublished - 1987
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Hemler, M. E., Huang, C., Takada, Y., Schwarz, L., Strominger, J. L., & Clabby, M. L. (1987). Characterization of the cell surface heterodimer VLA-4 and related peptides. Journal of Biological Chemistry, 262(24), 11478-11485.