Ras, Protein Kinase Cζ, and IκB Kinases 1 and 2 Are Downstream Effectors of CD44 During the Activation of NF-κB by Hyaluronic Acid Fragments in T-24 Carcinoma Cells

摘要: We have investigated the ability of hyaluronic acid (HA) fragments to activate transcription factor NF-kappa B. HA activated B in cell lines T-24, HeLa, MCF7, and J774. Further studies T-24 cells demonstrated that also induced I kappa alpha phosphorylation degradation, B-linked reporter gene expression, ICAM-1 promoter activity an B-dependent manner. The effect was size dependent as neither disaccharide nor native were active. CD44, principal cellular receptor for HA, critical response because anti-CD44 Ab IM7.8.1 blocked on kinase complex, a expressing dominant negative kinases 1 or 2. Activation protein C (PKC) required calphostin inhibited activation phosphorylation. In particular, PKC zeta transfection with expression increased activity. Furthermore, damnacanthal manumycin A, two mechanistically distinct inhibitors Ras, activation. Transfection Ras (RasN17) fragment-induced within 5 min. Taken together, these establish novel signal transduction cascade emanating from CD44 zeta,