| First Author | Vi L | Year | 2015 |
| Journal | J Invest Dermatol | Volume | 135 |
| Issue | 3 | Pages | 885-894 |
| PubMed ID | 25268583 | Mgi Jnum | J:218617 |
| Mgi Id | MGI:5618049 | Doi | 10.1038/jid.2014.427 |
| Citation | Vi L, et al. (2015) Modulation of Type II TGF-beta Receptor Degradation by Integrin-Linked Kinase. J Invest Dermatol 135(3):885-94 |
| abstractText | Cutaneous responses to injury, infection, and tumor formation involve the activation of resident dermal fibroblasts and subsequent transition to myofibroblasts. The key for induction of myofibroblast differentiation is the activation of transforming growth factor-beta (TGF-beta) receptors and stimulation of integrins and their associated proteins, including integrin-linked kinase (ILK). Cross-talk processes between TGF-beta and ILK are crucial for myofibroblast formation, as ILK-deficient dermal fibroblasts exhibit impaired responses to TGF-beta receptor stimulation. We now show that ILK associates with type II TGF-beta receptors (TbetaRII) in ligand- and receptor kinase activity-independent manners. In cells with targeted Ilk gene inactivation, cellular levels of TbetaRII are decreased, through mechanisms that involve enhanced ubiquitination and proteasomal degradation. Partitioning of TGF-beta receptors into membrane has been linked to proteasome-dependent receptor degradation. We found that interfering with membrane raft formation in ILK-deficient cells restored TbetaRII levels and signaling. These observations support a model whereby ILK functions in fibroblasts to direct TbetaRII away from degradative pathways during their differentiation into myofibroblasts. |
