title: Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction.
abstract: 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.
authors.affiliation: Department of Pathology, Edinburgh University Medical School, UK.
authors.forename: H-S
authors.initials: HS
authors.lastname: Lee
authors.forename: S J
authors.initials: SJ
authors.lastname: Millward-Sadler
authors.forename: M O
authors.initials: MO
authors.lastname: Wright
authors.forename: G
authors.initials: G
authors.lastname: Nuki
authors.forename: R
authors.initials: R
authors.lastname: Al-Jamal
authors.forename: D M
authors.initials: DM
authors.lastname: Salter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000201:enzymology*; D002460:Cell Line; D019902:Chondrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D040542:Mechanotransduction, Cellular; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D011312:Pressure; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D039641:Integrin beta Chains; D007527:Isoenzymes; D010455:Peptides; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C070301:peptide I; D011493:Protein Kinase C