The cerebral cavernous malformation proteins CCM2L and CCM2 prevent the activation of the MAP kinase MEKK3
Copyright policy )The cerebral cavernous malformation proteins CCM2L and CCM2 prevent the activation of the MAP kinase MEKK3
Significance The kinase MEKK3 (MAP3K) regulates cellular functions from proliferation to maintenance of cell identity, and plays an important role in cardiovascular development, yet little is known about how it is regulated. Loss-of-function mutations in CCM1 , CCM2 , or CCM3 cause cerebral cavernous malformations characterized by dilated, leaky blood vessels. CCM proteins form a complex and regulate the signal strength of several pathways. We demonstrate that CCM2 and CCM2-like (CCM2L), a recently described paralog, strongly prevented the activation of MEKK3 in vitro. In zebrafish, ccm2 and ccm2l genetically interacted to control cardiovascular development and body axis patterning during embryogenesis, and these were regulated by MEKK3. Therefore, two homologous CCM proteins regulate MEKK3 activity, and thus may modulate the strength of key signaling pathways.
- Brigham and Women's Faulkner Hospital United States
Transcription, Genetic, MAP Kinase Signaling System, Endothelial Cells, Cardiomegaly, MAP Kinase Kinase Kinase 3, Zebrafish Proteins, Enzyme Activation, Gene Knockdown Techniques, Multiprotein Complexes, Animals, Carrier Proteins, Mitogen-Activated Protein Kinase 7, Zebrafish
Transcription, Genetic, MAP Kinase Signaling System, Endothelial Cells, Cardiomegaly, MAP Kinase Kinase Kinase 3, Zebrafish Proteins, Enzyme Activation, Gene Knockdown Techniques, Multiprotein Complexes, Animals, Carrier Proteins, Mitogen-Activated Protein Kinase 7, Zebrafish
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).64 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!