Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction.
OBJECTIVE: The objective of this study was to examine PKC isozyme expression in human articular chondrocytes and assess roles for RACK1, a receptor for activated C kinase in the mechanotransduction process. METHODS: Primary cultures of human articular chondrocytes and a human chondrocyte cell line were studied for expression of PKC isozymes and RACK1 by western blotting. Following mechanical stimulation of chondrocytes in vitro in the absence or presence of anti-integrin antibodies and RGD containing oligopeptides, subcellular localization of PKCalpha and association of RACK1 with PKCalpha and beta1 integrin was assessed. RESULTS: Human articular chondrocytes express PKC isozymes alpha, gamma, delta, iota, and lambda. Following mechanical stimulation at 0.33Hz chondrocytes show a rapid, beta1 integrin dependent, translocation of PKCalpha to the cell membrane and increased association of RACK1 with PKCalpha and beta1 integrin. CONCLUSIONS: RACK1 mediated translocation of activated PKCalpha to the cell membrane and modulation of integrin-associated signaling are likely to be important in regulation of downstream signaling cascades controlling chondrocyte responses to mechanical stimuli.[1]References
- Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction. Lee, H.S., Millward-Sadler, S.J., Wright, M.O., Nuki, G., Al-Jamal, R., Salter, D.M. Osteoarthr. Cartil. (2002) [Pubmed]
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