Requirement of km23 for TGFbeta-mediated growth inhibition and induction of fibronectin expression.
We previously identified km23 as a novel TGFbeta receptor-interacting protein. Here we show that km23 is ubiquitously expressed in human tissues and that cell-type specific differences in endogenous km23 protein expression exist. In addition, we demonstrate that the phosphorylation of km23 is TGFbeta-dependent, in that EGF was unable to phosphorylate km23. Further, the kinase activity of both TGFbeta receptors appears to play a role in the TGFbeta-mediated phosphorylation of km23, although TGFbeta RII kinase activity is absolutely required for km23 phosphorylation. Blockade of km23 using small interfering RNAs significantly decreased key TGFbeta responses, including induction of fibronectin expression and inhibition of cell growth. Thus, our results demonstrate that km23 is required for TGFbeta induction of fibronectin expression and is necessary, but not sufficient, for TGFbeta-mediated growth inhibition.
Jin
Qunyan
Q
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Ding
Wei
W
Staub
Cory M
CM
Gao
Guofeng
G
Tang
Qian
Q
Mulder
Kathleen M
KM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D056445:Cytoplasmic Dyneins; D004285:Dogs; D004398:Dyneins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
C504797:DYNLRB1 protein, human; D005353:Fibronectins; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D056445:Cytoplasmic Dyneins; D004398:Dyneins