Deleted in liver cancer 1 (DLC1) is a Rho-GTPase-activating protein (GAP) that is downregulated in various tumor types. In vitro, DLC1 specifically inactivates the small GTPases RhoA, RhoB and RhoC through its GAP domain and this appears to contribute to its tumor suppressor function in vivo. Molecular mechanisms that control DLC1 activity have not so far been investigated. Here, we show that phorbol-ester-induced activation of protein kinase C and protein kinase D stimulates association of DLC1 with the phosphoserine/phosphothreonine-binding 14-3-3 adaptor proteins via recognition motifs that involve Ser327 and Ser431. Association with 14-3-3 proteins inhibits DLC1 GAP activity and facilitates signaling by active Rho. We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence. The binding to 14-3-3 proteins is thus a newly discovered mechanism by which DLC1 activity is regulated and compartmentalized.
%0 Journal Article
%1 Scholz2009
%A Scholz, Rolf-Peter
%A Regner, Jennifer
%A Theil, Anke
%A Erlmann, Patrik
%A Holeiter, Gerlinde
%A Jähne, Ruth
%A Schmid, Simone
%A Hausser, Angelika
%A Olayioye, Monilola a
%D 2009
%J Journal of cell science
%K 2008 hausser izi olayioye
%N Pt 1
%P 92--102
%R 10.1242/jcs.036251
%T DLC1 interacts with 14-3-3 proteins to inhibit RhoGAP activity and block nucleocytoplasmic shuttling.
%U https://www.ncbi.nlm.nih.gov/pubmed/19066281
%V 122
%X Deleted in liver cancer 1 (DLC1) is a Rho-GTPase-activating protein (GAP) that is downregulated in various tumor types. In vitro, DLC1 specifically inactivates the small GTPases RhoA, RhoB and RhoC through its GAP domain and this appears to contribute to its tumor suppressor function in vivo. Molecular mechanisms that control DLC1 activity have not so far been investigated. Here, we show that phorbol-ester-induced activation of protein kinase C and protein kinase D stimulates association of DLC1 with the phosphoserine/phosphothreonine-binding 14-3-3 adaptor proteins via recognition motifs that involve Ser327 and Ser431. Association with 14-3-3 proteins inhibits DLC1 GAP activity and facilitates signaling by active Rho. We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence. The binding to 14-3-3 proteins is thus a newly discovered mechanism by which DLC1 activity is regulated and compartmentalized.
%7 2008/12/11
%@ 0021-9533 (Print)$\backslash$n0021-9533 (Linking)
@article{Scholz2009,
abstract = {Deleted in liver cancer 1 (DLC1) is a Rho-GTPase-activating protein (GAP) that is downregulated in various tumor types. In vitro, DLC1 specifically inactivates the small GTPases RhoA, RhoB and RhoC through its GAP domain and this appears to contribute to its tumor suppressor function in vivo. Molecular mechanisms that control DLC1 activity have not so far been investigated. Here, we show that phorbol-ester-induced activation of protein kinase C and protein kinase D stimulates association of DLC1 with the phosphoserine/phosphothreonine-binding 14-3-3 adaptor proteins via recognition motifs that involve Ser327 and Ser431. Association with 14-3-3 proteins inhibits DLC1 GAP activity and facilitates signaling by active Rho. We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence. The binding to 14-3-3 proteins is thus a newly discovered mechanism by which DLC1 activity is regulated and compartmentalized.},
added-at = {2018-02-01T15:48:11.000+0100},
author = {Scholz, Rolf-Peter and Regner, Jennifer and Theil, Anke and Erlmann, Patrik and Holeiter, Gerlinde and J{\"{a}}hne, Ruth and Schmid, Simone and Hausser, Angelika and Olayioye, Monilola a},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2e6a0e2fb54a9a9e445f8b74d2d25d18a/cristiano},
doi = {10.1242/jcs.036251},
edition = {2008/12/11},
interhash = {f3e842c2d79b97dc2d2b729b7a0d82a1},
intrahash = {e6a0e2fb54a9a9e445f8b74d2d25d18a},
isbn = {0021-9533 (Print)$\backslash$n0021-9533 (Linking)},
issn = {0021-9533},
journal = {Journal of cell science},
keywords = {2008 hausser izi olayioye},
number = {Pt 1},
pages = {92--102},
pmid = {19066281},
timestamp = {2018-07-25T12:32:37.000+0200},
title = {{DLC1 interacts with 14-3-3 proteins to inhibit RhoGAP activity and block nucleocytoplasmic shuttling.}},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19066281},
volume = 122,
year = 2009
}
