Sequences within fibrinogen and intercellular adhesion molecule-1 (ICAM- 1) modulate signals required for mitogenesis

Elizabeth E. Gardiner, Stanley E. D'Souza

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30 Citations (Scopus)

Abstract

The interaction of fibrinogen (Fg) with intercellular adhesion molecule- 1 (ICAM) on B-lymphoid Raji cells results in mitogenesis (Gardiner, E. E., and D'Souza, S. E. (1997) J. Biol. Chem. 272, 15474-15480). Incubation of Raji with Fg resulted in the increased tyrosine phosphorylation of the receptor-associated tyrosine kinase, pp60(Src) and extracellular signal- regulated kinase-1 (ERK). The increase in ERK-1 phosphorylation was blocked by a peptide with sequence matching ICAM-1(8-22) and corresponded to a decrease in ERK-1 enzymatic activity. 100 μM amounts of Fg peptide γ-(117- 133) caused an increase in tyrosine phosphorylation of ERK-1. These results are consistent with our previous report wherein ICAM-1-(8-22) blocked Fg- induced mitogenesis and Fg-γ-(117-133) induced proliferation in Raji. The specific inhibitor of MEK, PD98059 (25 μM), abrogated the increased phosphorylation of ERK-1 and blocked Raji mitogenesis by >50%. Inhibitors of pp60(Src), geldanamycin (62 nM), and herbimycin A (2.5 μM) blocked >50% of Raji proliferation. These results indicate that the proliferation induced by Fg interactions with ICAM-1 is mediated in part by receptor-associated tyrosine kinases and ERK-1, and that the recognition sequences within Fg and ICAM-1 participate in the signaling process.

Original languageEnglish
Pages (from-to)11930-11936
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number17
DOIs
Publication statusPublished - 23 Apr 1999
Externally publishedYes

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