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Published on: July 10, 2019
Src family kinases promote vessel stability by antagonizing the Rho/ROCK pathway
1Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts 02114, USA.
Abstract:
Src family kinases (SFKs) are one of the signaling enzymes that contribute to angiogenesis, but their precise input to the various phases of the angiogenic program has not been defined. Using an in vitro model system, we discovered that SFKs promoted the formation of tubes and prevented their regression. They suppressed regression by activating the ERK pathway that antagonized the Rho/ROCK pathway, which was essential for regression. These studies reveal that SFKs contribute to several phases of the angiogenic program and identify the downstream effectors by which SFKs stabilize tubes.
Insights
Src family kinases (SFKs) promote tube formation and prevent regression during angiogenesis. They achieve this by activating the ERK pathway, which counteracts the Rho/ROCK pathway essential for tube regression, stabilizing new blood vessels.
Area of Science:
- Cell signaling
- Molecular biology
- Angiogenesis research
Background:
- Src family kinases (SFKs) are implicated in angiogenesis.
- The specific roles of SFKs in different angiogenic phases remain unclear.
Purpose of the Study:
- To elucidate the precise role of SFKs in angiogenesis.
- To identify downstream signaling pathways regulated by SFKs during tube formation and stabilization.
Main Methods:
- Utilized an in vitro model system to study angiogenesis.
- Investigated the activation of ERK and Rho/ROCK pathways.
Main Results:
- SFKs were found to promote endothelial tube formation.
- SFKs inhibited tube regression by activating the ERK pathway.
- The ERK pathway was shown to antagonize the Rho/ROCK pathway, which is critical for regression.
Conclusions:
- SFKs play a crucial role in multiple stages of angiogenesis.
- SFKs stabilize newly formed vascular tubes by modulating ERK and Rho/ROCK signaling.
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