Evolving a robust signal transduction pathway from weak cross-talk
We have evolved a robust two‐component signal transduction pathway from a sensor kinase (SK) and non‐partner response regulator (RR) that show weak cross‐talk in vitro and no detectable cross‐talk in vivo in wild‐type strains. The SK, CpxA, is bifunctional, with both kinase and phosphatase activitie...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/84667 https://orcid.org/0000-0002-8288-7607 |
| _version_ | 1826211109725536256 |
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| author | Siryaporn, Albert Goulian, Mark Perchuk, Barrett Laub, Michael T |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Siryaporn, Albert Goulian, Mark Perchuk, Barrett Laub, Michael T |
| author_sort | Siryaporn, Albert |
| collection | MIT |
| description | We have evolved a robust two‐component signal transduction pathway from a sensor kinase (SK) and non‐partner response regulator (RR) that show weak cross‐talk in vitro and no detectable cross‐talk in vivo in wild‐type strains. The SK, CpxA, is bifunctional, with both kinase and phosphatase activities for its partner RR. We show that by combining a small number of mutations in CpxA that individually increase phosphorylation of the non‐partner RR OmpR, phosphatase activity against phospho‐OmpR emerges. The resulting circuit also becomes responsive to input signal to CpxA. The effects of combining these mutations in CpxA appear to reflect complex intragenic interactions between multiple sites in the protein. However, by analyzing a simple model of two‐component signaling, we show that the behavior can be explained by a monotonic change in a single parameter controlling protein–protein interaction strength. The results suggest one possible mode of evolution for two‐component systems with bifunctional SKs whereby the remarkable properties and competing reactions that characterize these systems can emerge by combining mutations of the same effect. |
| first_indexed | 2024-09-23T15:01:02Z |
| format | Article |
| id | mit-1721.1/84667 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:01:02Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/846672022-09-29T12:03:52Z Evolving a robust signal transduction pathway from weak cross-talk Siryaporn, Albert Goulian, Mark Perchuk, Barrett Laub, Michael T Massachusetts Institute of Technology. Department of Biology Perchuk, Barrett Laub, Michael T. We have evolved a robust two‐component signal transduction pathway from a sensor kinase (SK) and non‐partner response regulator (RR) that show weak cross‐talk in vitro and no detectable cross‐talk in vivo in wild‐type strains. The SK, CpxA, is bifunctional, with both kinase and phosphatase activities for its partner RR. We show that by combining a small number of mutations in CpxA that individually increase phosphorylation of the non‐partner RR OmpR, phosphatase activity against phospho‐OmpR emerges. The resulting circuit also becomes responsive to input signal to CpxA. The effects of combining these mutations in CpxA appear to reflect complex intragenic interactions between multiple sites in the protein. However, by analyzing a simple model of two‐component signaling, we show that the behavior can be explained by a monotonic change in a single parameter controlling protein–protein interaction strength. The results suggest one possible mode of evolution for two‐component systems with bifunctional SKs whereby the remarkable properties and competing reactions that characterize these systems can emerge by combining mutations of the same effect. National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Award DMR0520020) 2014-02-07T14:34:09Z 2014-02-07T14:34:09Z 2010-12 2010-06 Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/84667 Siryaporn, Albert, Barrett S Perchuk, Michael T Laub, and Mark Goulian. “Evolving a robust signal transduction pathway from weak cross-talk.” Molecular Systems Biology 6 (December 21, 2010). Copyright © 2010 EMBO and Macmillan Publishers Limited https://orcid.org/0000-0002-8288-7607 en_US http://dx.doi.org/10.1038/msb.2010.105 Molecular Systems Biology Creative Commons Attribution‐NonCommercial License http://creativecommons.org/licenses/by-nc/3.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Siryaporn, Albert Goulian, Mark Perchuk, Barrett Laub, Michael T Evolving a robust signal transduction pathway from weak cross-talk |
| title | Evolving a robust signal transduction pathway from weak cross-talk |
| title_full | Evolving a robust signal transduction pathway from weak cross-talk |
| title_fullStr | Evolving a robust signal transduction pathway from weak cross-talk |
| title_full_unstemmed | Evolving a robust signal transduction pathway from weak cross-talk |
| title_short | Evolving a robust signal transduction pathway from weak cross-talk |
| title_sort | evolving a robust signal transduction pathway from weak cross talk |
| url | http://hdl.handle.net/1721.1/84667 https://orcid.org/0000-0002-8288-7607 |
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