Sequences within fibrinogen and intercellular adhesion molecule-1 (ICAM-1) modulate signals required for mitogenesis.
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 microM amounts of Fg peptide gamma-(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-gamma-(117-133) induced proliferation in Raji. The specific inhibitor of MEK, PD98059 (25 microM), 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 microM) 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.
Gardiner
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EE
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
D'Souza
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SE
D000595:Amino Acid Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008934:Mitogens / Q000378:metabolism*; D008969:Molecular Sequence Data; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D008934:Mitogens; D018799:Intercellular Adhesion Molecule-1; D014443:Tyrosine; D005340:Fibrinogen; D015688:Oncogene Protein pp60(v-src); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases