J Biol Chem 2011,
PMID: 21784851
Nho, Richard Seonghun; Peterson, Mark
Human lung fibroblasts utilize integrins to attach and proliferate on type I collagen. β1 integrin is the major integrin subunit for this attachment. Integrins coordinate cellular responses to cell-cell and cell-extracellular matrix interactions that regulate a variety of biological processes. Although β1 integrin-mediated signaling pathways in lung fibroblasts have been studied, a detailed molecular mechanism regulating translational control of gene expression by 4EBP-1 is not understood. 4EBP-1 inhibits cap-dependent translation by binding to the eIF4E translation initiation factor. We found that when lung fibroblasts attach to collagen via β1 integrin, high Src activity suppresses 4EBP-1 expression via PP2A, and the decrease of 4EBP-1 is due to protein degradation. The inhibition of Src activity dramatically increases PP2A and 4EBP-1 expression. Furthermore ectopic expression of PP2A, or PP2A silencing using PP2A siRNA confirmed that 4EBP-1 is regulated by PP2A. In addition, we found that 4EBP-1 inhibition by fibroblast attachment to collagen increases cap-dependent translation. Our study showed that when lung fibroblasts are attached to collagen matrix, the β1 integrin/Src/PP2A-mediated 4EBP-1 regulatory pathway is activated. We suggest that β1 integrin-mediated signaling pathway may be a crucial event in regulating fibroblast translational control machinery on collagen matrix.
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Text Mining Data
4EBP-1 ⊣ Src: "
We found that when lung fibroblasts attach to collagen via ß1 integrin, high
Src activity
suppresses 4EBP-1 expression via PP2A, and the decrease of 4EBP-1 is due to protein degradation
"
4EBP-1 ⊣ Src: "
The inhibition of Src activity dramatically increases PP2A and 4EBP-1 expression
"
PP2A ⊣ Src: "
The inhibition of Src activity dramatically increases PP2A and 4EBP-1 expression
"
4EBP-1 → PP2A: "
Furthermore ectopic expression of PP2A, or PP2A silencing using PP2A siRNA confirmed that 4EBP-1 is regulated by PP2A
"
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