PH motifs in PAR1&2 endow breast cancer growth

A. Kancharla, M. Maoz, M. Jaber, D. Agranovich, T. Peretz, S. Grisaru-Granovsky, B. Uziely and R. Bar-Shavit ()
Additional contact information
A. Kancharla: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center Jerusalem
M. Maoz: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center Jerusalem
M. Jaber: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center Jerusalem
D. Agranovich: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center Jerusalem
T. Peretz: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center Jerusalem
S. Grisaru-Granovsky: Hebrew-University
B. Uziely: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center Jerusalem
R. Bar-Shavit: Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center Jerusalem

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Although emerging roles of protease-activated receptor1&2 (PAR1&2) in cancer are recognized, their underlying signalling events are poorly understood. Here we show signal-binding motifs in PAR1&2 that are critical for breast cancer growth. This occurs via the association of the pleckstrin homology (PH) domain with Akt/PKB as a key signalling event of PARs. Other PH-domain signal-proteins such as Etk/Bmx and Vav3 also associate with PAR1 and PAR2 through their PH domains. PAR1 and PAR2 bind with priority to Etk/Bmx. A point mutation in PAR2, H349A, but not in R352A, abrogates PH-protein association and is sufficient to markedly reduce PAR2-instigated breast tumour growth in vivo and placental extravillous trophoblast (EVT) invasion in vitro. Similarly, the PAR1 mutant hPar1-7A, which is unable to bind the PH domain, reduces mammary tumours and EVT invasion, endowing these motifs with physiological significance and underscoring the importance of these previously unknown PAR1 and PAR2 PH-domain-binding motifs in both pathological and physiological invasion processes.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9853 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9853

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9853

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().