Serine-71 phosphorylation of Rac1 modulates downstream signaling.
The Rho GTPases Rac1 and Cdc42 regulate a variety of cellular functions by signaling to different signal pathways. It is believed that the presence of a specific effector at the location of GTPase activation determines the route of downstream signaling. We previously reported about EGF-induced Ser-7...
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2012
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oai:doaj.org-article:5e44924797cc488a8fbeaeddd3ecf3742021-11-18T07:06:11ZSerine-71 phosphorylation of Rac1 modulates downstream signaling.1932-620310.1371/journal.pone.0044358https://doaj.org/article/5e44924797cc488a8fbeaeddd3ecf3742012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22970203/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The Rho GTPases Rac1 and Cdc42 regulate a variety of cellular functions by signaling to different signal pathways. It is believed that the presence of a specific effector at the location of GTPase activation determines the route of downstream signaling. We previously reported about EGF-induced Ser-71 phosphorylation of Rac1/Cdc42. By using the phosphomimetic S71E-mutants of Rac1 and Cdc42 we investigated the impact of Ser-71 phosphorylation on binding to selected effector proteins. Binding of the constitutively active (Q61L) variants of Rac1 and Cdc42 to their specific interaction partners Sra-1 and N-WASP, respectively, as well as to their common effector protein PAK was abrogated when Ser-71 was exchanged to glutamate as phosphomimetic substitution. Interaction with their common effector proteins IQGAP1/2/3 or MRCK alpha was, however, hardly affected. This ambivalent behaviour was obvious in functional assays. In contrast to Rac1 Q61L, phosphomimetic Rac1 Q61L/S71E was not able to induce increased membrane ruffling. Instead, Rac1 Q61L/S71E allowed filopodia formation, which is in accordance with abrogation of the dominant Sra-1/Wave signalling pathway. In addition, in contrast to Rac1 transfected cells Rac1 S71E failed to activate PAK1/2. On the other hand, Rac1 Q61L/S71E was as effective in activation of NF-kappaB as Rac1 Q61L, illustrating positive signal transduction of phosphorylated Rac1. Together, these data suggest that phosphorylation of Rac1 and Cdc42 at serine-71 represents a reversible mechanism to shift specificity of GTPase/effector coupling, and to preferentially address selected downstream pathways.Janett SchwarzJulia ProffAnika HävemeierMarkus LadweinKlemens RottnerBritta BarlagAndreas PichHelma TatgeIngo JustRalf GerhardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44358 (2012) |
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Medicine R Science Q Janett Schwarz Julia Proff Anika Hävemeier Markus Ladwein Klemens Rottner Britta Barlag Andreas Pich Helma Tatge Ingo Just Ralf Gerhard Serine-71 phosphorylation of Rac1 modulates downstream signaling. |
| description |
The Rho GTPases Rac1 and Cdc42 regulate a variety of cellular functions by signaling to different signal pathways. It is believed that the presence of a specific effector at the location of GTPase activation determines the route of downstream signaling. We previously reported about EGF-induced Ser-71 phosphorylation of Rac1/Cdc42. By using the phosphomimetic S71E-mutants of Rac1 and Cdc42 we investigated the impact of Ser-71 phosphorylation on binding to selected effector proteins. Binding of the constitutively active (Q61L) variants of Rac1 and Cdc42 to their specific interaction partners Sra-1 and N-WASP, respectively, as well as to their common effector protein PAK was abrogated when Ser-71 was exchanged to glutamate as phosphomimetic substitution. Interaction with their common effector proteins IQGAP1/2/3 or MRCK alpha was, however, hardly affected. This ambivalent behaviour was obvious in functional assays. In contrast to Rac1 Q61L, phosphomimetic Rac1 Q61L/S71E was not able to induce increased membrane ruffling. Instead, Rac1 Q61L/S71E allowed filopodia formation, which is in accordance with abrogation of the dominant Sra-1/Wave signalling pathway. In addition, in contrast to Rac1 transfected cells Rac1 S71E failed to activate PAK1/2. On the other hand, Rac1 Q61L/S71E was as effective in activation of NF-kappaB as Rac1 Q61L, illustrating positive signal transduction of phosphorylated Rac1. Together, these data suggest that phosphorylation of Rac1 and Cdc42 at serine-71 represents a reversible mechanism to shift specificity of GTPase/effector coupling, and to preferentially address selected downstream pathways. |
| format |
article |
| author |
Janett Schwarz Julia Proff Anika Hävemeier Markus Ladwein Klemens Rottner Britta Barlag Andreas Pich Helma Tatge Ingo Just Ralf Gerhard |
| author_facet |
Janett Schwarz Julia Proff Anika Hävemeier Markus Ladwein Klemens Rottner Britta Barlag Andreas Pich Helma Tatge Ingo Just Ralf Gerhard |
| author_sort |
Janett Schwarz |
| title |
Serine-71 phosphorylation of Rac1 modulates downstream signaling. |
| title_short |
Serine-71 phosphorylation of Rac1 modulates downstream signaling. |
| title_full |
Serine-71 phosphorylation of Rac1 modulates downstream signaling. |
| title_fullStr |
Serine-71 phosphorylation of Rac1 modulates downstream signaling. |
| title_full_unstemmed |
Serine-71 phosphorylation of Rac1 modulates downstream signaling. |
| title_sort |
serine-71 phosphorylation of rac1 modulates downstream signaling. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/5e44924797cc488a8fbeaeddd3ecf374 |
| work_keys_str_mv |
AT janettschwarz serine71phosphorylationofrac1modulatesdownstreamsignaling AT juliaproff serine71phosphorylationofrac1modulatesdownstreamsignaling AT anikahavemeier serine71phosphorylationofrac1modulatesdownstreamsignaling AT markusladwein serine71phosphorylationofrac1modulatesdownstreamsignaling AT klemensrottner serine71phosphorylationofrac1modulatesdownstreamsignaling AT brittabarlag serine71phosphorylationofrac1modulatesdownstreamsignaling AT andreaspich serine71phosphorylationofrac1modulatesdownstreamsignaling AT helmatatge serine71phosphorylationofrac1modulatesdownstreamsignaling AT ingojust serine71phosphorylationofrac1modulatesdownstreamsignaling AT ralfgerhard serine71phosphorylationofrac1modulatesdownstreamsignaling |
| _version_ |
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