The role of betagamma and alphagamma complexes in the assembly of human fibrinogen.
The role of alphagamma and betagamma dimers as intermediates in the assembly of fibrinogen was examined in cell fusion experiments using stably transfected baby hamster kidney cell lines expressing one or combinations of fibrinogen chains. Fibrinogen was readily formed and secreted into the culture media when cells co-expressing beta and gamma chains and generating betagamma complexes were fused with cells expressing only the alpha chain. Likewise, when cells co-expressing alpha and gamma chains and generating alphagamma complexes were fused with cells expressing only the beta chain, fibrinogen was also formed and secreted. The relative amounts of alphagamma or betagamma intermediates observed during fibrinogen biosynthesis were determined by the levels of the component chains; i.e. when the beta chain was limiting, the alphagamma dimer was the predominant intermediate; likewise, when the alpha chain was limiting, the betagamma complex was the predominant intermediate. The incorporation of preformed alphagamma and betagamma complexes into secreted fibrinogen did not require concurrent protein synthesis, as shown by experiments employing cycloheximide. These data strongly support the role of alphagamma and betagamma complexes as functional intermediates in the assembly of fibrinogen.
Department of Biochemistry, University of Washington, Seattle, Washington 98195-7350, USA.
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Davie
D000818:Animals; D006528:Carcinoma, Hepatocellular; D002459:Cell Fusion; D002460:Cell Line; D006224:Cricetinae; D019281:Dimerization; D005340:Fibrinogen / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D046911:Macromolecular Substances; D011092:Polyethylene Glycols / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D014162:Transfection
D046911:Macromolecular Substances; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D005340:Fibrinogen