Affiliation:
1. From the Department of Physiopathology and Human Molecular Genetics, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
Abstract
AbstractThis work reports the establishment of a Chinese hamster ovary (CHO) cell line stably coexpressing the human αIIbβ3 integrin and the platelet-activating factor receptor (PAFR). These cells aggregate in response to PAF in a Ca++, αIIbβ3, and soluble fibrinogen (Fg)–dependent manner that is prevented by PAF antagonists or αIIbβ3 blockade. The aggregating response is accompanied by enhanced binding of fibrinogen and the activation-dependent IgM PAC1. This model has permitted us to identify, for the first time, intracellular signals distinctly associated with either αIIbβ3-mediated adhesion or aggregation. Nonreceptor activation of protein kinase C (PKC) by phorbol ester produced cellular adhesion and spreading onto immobilized Fg, but it was not a sufficient signal to provoke cellular aggregation. Moreover, inhibition of PKC impeded the PAF stimulation of cellular adhesion, whereas the aggregation was not prevented. The PAF-induced cellular aggregation was distinctly associated with signaling events arising from the liganded Fg receptor and the agonist-induced stimulation of a calcium/calmodulin-dependent signaling pathway. Sustained tyrosine phosphorylation of both mitogen-activated protein kinase (MAPK) and an approximately 100-kd protein was associated with the PAF-induced aggregation, whereas phosphorylation of focal adhesion kinase (FAK) was preferably associated with cellular adherence and spreading onto immobilized Fg.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
9 articles.
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