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see Table to the right

The phosphorelay is a complex variation of a two-component regulatory system. It includes phosphotransferases that transfer the phosphoryl group from the sensor kinases to the ultimate target. The sporulation initiation phosphorelay is the paradigm of this class of signal transduction systems.

The kinases

Proteins controlliing the activity of the kinases

The phosphotransferases

The ultimate target

Phosphatases controlling the phosphorelay (and peptides that modulate their activity)

Other protein controlling the activity of the phosphorelay

A mathematical model

Heiko Babel, Ilka B Bischofs
Molecular and cellular factors control signal transduction via switchable allosteric modulator proteins (SAMPs).
BMC Syst Biol: 2016, 10;35
[PubMed:27122155] [] [DOI] (I e)

Adaoha E C Ihekwaba, Ivan Mura, Gary C Barker
Computational modelling and analysis of the molecular network regulating sporulation initiation in Bacillus subtilis.
BMC Syst Biol: 2014, 8;119
[PubMed:25341802] [] [DOI] (I e)

Sara Jabbari, John T Heap, John R King
Mathematical modelling of the sporulation-initiation network in Bacillus subtilis revealing the dual role of the putative quorum-sensing signal molecule PhrA.
Bull. Math. Biol.: 2011, 73(1);181-211
[PubMed:20238180] [] [DOI] (I p)


Richard Losick
Concerns about Continuing Claims that a Protein Complex Interacts with the Phosphorelay.
mBio: 2020, 11(2);
[PubMed:32156829] [] [DOI] (I e)

David Dubnau
Reply to Losick, "Concerns about Continuing Claims that a Protein Complex Interacts with the Phosphorelay".
mBio: 2020, 11(2);
[PubMed:32156813] [] [DOI] (I e)

Jatin Narula, Masaya Fujita, Oleg A Igoshin
Functional requirements of cellular differentiation: lessons from Bacillus subtilis.
Curr. Opin. Microbiol.: 2016, 34;38-46
[PubMed:27501460] [] [DOI] (I p)

Daniel Schultz
Coordination of cell decisions and promotion of phenotypic diversity in B. subtilis via pulsed behavior of the phosphorelay.
Bioessays: 2016, 38(5);440-5
[PubMed:26941227] [] [DOI] (I p)

Peter Dürre
Ancestral sporulation initiation.
Mol. Microbiol.: 2011, 80(3);584-7
[PubMed:21435030] [] [DOI] (I p)

Imke G de Jong, Jan-Willem Veening, Oscar P Kuipers
Heterochronic phosphorelay gene expression as a source of heterogeneity in Bacillus subtilis spore formation.
J. Bacteriol.: 2010, 192(8);2053-67
[PubMed:20154131] [] [DOI] (I p)

Ruth E Silversmith
Auxiliary phosphatases in two-component signal transduction.
Curr. Opin. Microbiol.: 2010, 13(2);177-83
[PubMed:20133180] [] [DOI] (I p)

Daniel Schultz, Peter G Wolynes, Eshel Ben Jacob, José N Onuchic
Deciding fate in adverse times: sporulation and competence in Bacillus subtilis.
Proc. Natl. Acad. Sci. U.S.A.: 2009, 106(50);21027-34
[PubMed:19995980] [] [DOI] (I p)

Daelynn R Buelow, Tracy L Raivio
Three (and more) component regulatory systems - auxiliary regulators of bacterial histidine kinases.
Mol. Microbiol.: 2010, 75(3);547-66
[PubMed:19943903] [] [DOI] (I p)

Keith Stephenson, James A Hoch
Evolution of signalling in the sporulation phosphorelay.
Mol. Microbiol.: 2002, 46(2);297-304
[PubMed:12406209] [] [DOI] (P p)

M Perego, J A Brannigan
Pentapeptide regulation of aspartyl-phosphate phosphatases.
Peptides: 2001, 22(10);1541-7
[PubMed:11587783] [] [DOI] (P p)

J A Hoch, K I Varughese
Keeping signals straight in phosphorelay signal transduction.
J. Bacteriol.: 2001, 183(17);4941-9
[PubMed:11489844] [] [DOI] (P p)

J A Hoch
Two-component and phosphorelay signal transduction.
Curr. Opin. Microbiol.: 2000, 3(2);165-70
[PubMed:10745001] [] [DOI] (P p)

M Perego
Kinase-phosphatase competition regulates Bacillus subtilis development.
Trends Microbiol.: 1998, 6(9);366-70
[PubMed:9778730] [] [DOI] (P p)

M Perego, P Glaser, J A Hoch
Aspartyl-phosphate phosphatases deactivate the response regulator components of the sporulation signal transduction system in Bacillus subtilis.
Mol. Microbiol.: 1996, 19(6);1151-7
[PubMed:8730857] [] [DOI] (P p)

J A Hoch
The phosphorelay signal transduction pathway in the initiation of Bacillus subtilis sporulation.
J. Cell. Biochem.: 1993, 51(1);55-61
[PubMed:8432743] [] [DOI] (P p)

K Trach, D Burbulys, M Strauch, J J Wu, N Dhillon, R Jonas, C Hanstein, P Kallio, M Perego, T Bird
Control of the initiation of sporulation in Bacillus subtilis by a phosphorelay.
Res. Microbiol.: 1991, 142(7-8);815-23
[PubMed:1664534] [] [DOI] (P p)

Important original publications

Philip Davidson, Rory Eutsey, Brendan Redler, N Luisa Hiller, Michael T Laub, Dannie Durand
Flexibility and constraint: Evolutionary remodeling of the sporulation initiation pathway in Firmicutes.
PLoS Genet.: 2018, 14(9);e1007470
[PubMed:30212463] [] [DOI] (I e)

Jatin Narula, Anna Kuchina, Fang Zhang, Masaya Fujita, Gürol M Süel, Oleg A Igoshin
Slowdown of growth controls cellular differentiation.
Mol. Syst. Biol.: 2016, 12(5);871
[PubMed:27216630] [] [DOI] (I e)

Jatin Narula, Anna Kuchina, Dong-Yeon D Lee, Masaya Fujita, Gürol M Süel, Oleg A Igoshin
Chromosomal Arrangement of Phosphorelay Genes Couples Sporulation and DNA Replication.
Cell: 2015, 162(2);328-337
[PubMed:26165942] [] [DOI] (I p)

Jatin Narula, Seram N Devi, Masaya Fujita, Oleg A Igoshin
Ultrasensitivity of the Bacillus subtilis sporulation decision.
Proc. Natl. Acad. Sci. U.S.A.: 2012, 109(50);E3513-22
[PubMed:23169620] [] [DOI] (I p)

Anna Kuchina, Lorena Espinar, Tolga Çağatay, Alejandro O Balbin, Fang Zhang, Alma Alvarado, Jordi Garcia-Ojalvo, Gürol M Süel
Temporal competition between differentiation programs determines cell fate choice.
Mol. Syst. Biol.: 2011, 7;557
[PubMed:22146301] [] [DOI] (I e)

Anna L McLoon, Ilana Kolodkin-Gal, Shmuel M Rubinstein, Roberto Kolter, Richard Losick
Spatial regulation of histidine kinases governing biofilm formation in Bacillus subtilis.
J. Bacteriol.: 2011, 193(3);679-85
[PubMed:21097618] [] [DOI] (I p)

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