We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A Screen for PKN3 Substrates Reveals an Activating Phosphorylation of ARHGAP18.
- Authors
Dibus, Michal; Brábek, Jan; Rösel, Daniel
- Abstract
Protein kinase N3 (PKN3) is a serine/threonine kinase implicated in tumor progression of multiple cancer types, however, its substrates and effector proteins still remain largely understudied. In the present work we aimed to identify novel PKN3 substrates in a phosphoproteomic screen using analog sensitive PKN3. Among the identified putative substrates we selected ARHGAP18, a protein from RhoGAP family, for validation of the screen and further study. We confirmed that PKN3 can phosphorylate ARHGAP18 in vitro and we also characterized the interaction of the two proteins, which is mediated via the N-terminal part of ARHGAP18. We present strong evidence that PKN3-ARHGAP18 interaction is increased upon ARHGAP18 phosphorylation and that the phosphorylation of ARHGAP18 by PKN3 enhances its GAP domain activity and contributes to negative regulation of active RhoA. Taken together, we identified new set of potential PKN3 substrates and revealed a new negative feedback regulatory mechanism of Rho signaling mediated by PKN3-induced ARHGAP18 activation.
- Subjects
PHOSPHORYLATION; SERINE/THREONINE kinases; PROTEIN kinases; CANCER invasiveness; MULTIPLE tumors; PROTEIN-protein interactions
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 20, p7769
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21207769