Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In epidermal wounds, precursor laminin 5 (alpha3beta3gamma2) is deposited in the provisional basement membrane (PBM) before other BM components. Precursor laminin 5 contains G4/5 globular domains at the carboxyl terminus of the alpha3 chain. Here, the function of G4/5 was evaluated in deposition of laminin 5. Soluble laminin 5, secreted by keratinocytes in culture, is cleaved by an endogenous protease releasing G4/5. Thrombin, a serum protease, cleaves G4/5 indistinguishably from endogenous protease. Soluble human precursor laminin 5, but not cleaved laminin 5, was bound and deposited by mouse keratinocytes null for mouse alpha3 chain (alpha3-/- MKs). The deposition rescued adhesion and spreading and survival. In a model for PBM assembly, precursor laminin 5 was deposited along fibronectin fibrils at the junction between co-cultures of keratinocytes and fibroblasts. In both models, the deposition of precursor laminin 5 was inhibited by removal of G4/5 with thrombin. To confirm that G4/5 participates in deposition, the human LAMA3A gene was modified to produce alpha3 chains either without or with G4/5 that cannot be cleaved. Both precleaved and noncleavable alpha3 isoforms were expressed in alpha3-/- MKs, where they deposited sufficiently to rescue adhesion via integrins alpha3beta1 and alpha6beta4. Despite this similarity, noncleavable laminin 5 was at least threefold more efficiently deposited than precleaved isoform. We conclude that the G4/5 domain in the alpha3 chain facilitates deposition of precursor laminin 5 into the PBM in epidermal wounds.
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PMID:Globular domains 4/5 of the laminin alpha3 chain mediate deposition of precursor laminin 5. 1531 72