TY - JOUR
T1 - Sequences within fibrinogen and intercellular adhesion molecule-1 (ICAM- 1) modulate signals required for mitogenesis
AU - Gardiner, Elizabeth E.
AU - D'Souza, Stanley E.
PY - 1999/4/23
Y1 - 1999/4/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033597116&partnerID=8YFLogxK
U2 - 10.1074/jbc.274.17.11930
DO - 10.1074/jbc.274.17.11930
M3 - Article
SN - 0021-9258
VL - 274
SP - 11930
EP - 11936
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 17
ER -