MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions

DSpace/Manakin Repository

MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions

Citable link to this page

 

 
Title: MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions
Author: Duval, Damien; Labbé, Pauline; Bureau, Léa; Le Tourneau, Thierry; Norris, Russell A.; Markwald, Roger R.; Levine, Robert; Schott, Jean-Jacques; Mérot, Jean

Note: Order does not necessarily reflect citation order of authors.

Citation: Duval, Damien, Pauline Labbé, Léa Bureau, Thierry Le Tourneau, Russell A. Norris, Roger R. Markwald, Robert Levine, Jean-Jacques Schott, and Jean Mérot. 2015. “MVP-Associated Filamin A Mutations Affect FlnA-PTPN12 (PTP-PEST) Interactions.” Journal of cardiovascular development and disease 2 (3): 233-247. doi:10.3390/jcdd2030233. http://dx.doi.org/10.3390/jcdd2030233.
Full Text & Related Files:
Abstract: Although the genetic basis of mitral valve prolapse (MVP) has now been clearly established, the molecular and cellular mechanisms involved in the pathological processes associated to a specific mutation often remain to be determined. The FLNA gene (encoding Filamin A; FlnA) was the first gene associated to non-syndromic X-linked myxomatous valvular dystrophy, but the impacts of the mutations on its function remain un-elucidated. Here, using the first repeats (1–8) of FlnA as a bait in a yeast two-hybrid screen, we identified the tyrosine phosphatase PTPN12 (PTP-PEST) as a specific binding partner of this region of FlnA protein. In addition, using yeast two-hybrid trap assay pull down and co-immunoprecipitation experiments, we showed that the MVP-associated FlnA mutations (G288R, P637Q, H743P) abolished FlnA/PTPN12 interactions. PTPN12 is a key regulator of signaling pathways involved in cell-extracellular matrix (ECM) crosstalk, cellular responses to mechanical stress that involve integrins, focal adhesion transduction pathways, and actin cytoskeleton dynamics. Interestingly, we showed that the FlnA mutations impair the activation status of two PTPN12 substrates, the focal adhesion associated kinase Src, and the RhoA specific activating protein p190RhoGAP. Together, these data point to PTPN12/FlnA interaction and its weakening by FlnA mutations as a mechanism potentially involved in the physiopathology of FlnA-associated MVP.
Published Version: doi:10.3390/jcdd2030233
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654411/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845162
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters