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Repetto, M.V.; Winters, M.J.; Bush, A.; Reiter, W.; Hollenstein, D.M.; Ammerer, G.; Pryciak, P.M.; Colman-Lerner, A. "CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5" (2018) Molecular Cell. 69(6):938-952.e6
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Abstract:

We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages. Surprisingly, in S phase, where Ste5 recruitment should be blocked, we observed an initial recruitment followed by a steep drop-off. This delayed inhibition revealed a requirement for both CDK activity and negative feedback from the pathway MAPK Fus3. Mutagenesis, mass spectrometry, and electrophoretic analyses suggest that the CDK and MAPK modify shared sites, which are most extensively phosphorylated when both kinases are active and able to bind their docking sites on Ste5. Such collaborative phosphorylation can broaden regulatory inputs and diversify output dynamics of signaling pathways. CDKs and MAPKs phosphorylate similar sites yet generally have distinct functions and substrates. Repetto et al. uncover a case where these kinases collaborate to regulate a substrate in a signal transduction pathway by phosphorylating a shared set of sites. © 2018 Elsevier Inc.

Registro:

Documento: Artículo
Título:CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5
Autor:Repetto, M.V.; Winters, M.J.; Bush, A.; Reiter, W.; Hollenstein, D.M.; Ammerer, G.; Pryciak, P.M.; Colman-Lerner, A.
Filiación:Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Buenos Aires, C1428EGA, Argentina
CONICET-UBA, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires C1428EHA, Argentina
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, United States
Department for Biochemistry, Max F. Perutz Laboratories, University of Vienna, Vienna, 1030, Austria
Palabras clave:Cdc28; Cks1; Cln2; cyclin; G protein; mating; pheromone; signal transduction; start; Ste4; cyclin dependent kinase; mitogen activated protein kinase; scaffold protein; ste5 protein; unclassified drug; CLN1 protein, S cerevisiae; CLN2 protein, S cerevisiae; cyclin dependent kinase; cycline; FUS3 protein, S cerevisiae; mitogen activated protein kinase; protein binding; Saccharomyces cerevisiae protein; signal transducing adaptor protein; STE5 protein, S cerevisiae; Article; cell cycle S phase; G1 phase cell cycle checkpoint; intracellular signaling; MAPK signaling; mass spectrometry; molecular docking; mutagenesis; negative feedback; protein binding; protein electrophoresis; protein phosphorylation; regulatory mechanism; time-lapse microscopy; binding site; cell cycle checkpoint; cell membrane; enzyme specificity; enzymology; genetics; growth, development and aging; kinetics; metabolism; phosphorylation; Saccharomyces cerevisiae; signal transduction; Adaptor Proteins, Signal Transducing; Binding Sites; Cell Cycle Checkpoints; Cell Membrane; Cyclin-Dependent Kinases; Cyclins; Kinetics; Mitogen-Activated Protein Kinases; Phosphorylation; Protein Binding; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Substrate Specificity
Año:2018
Volumen:69
Número:6
Página de inicio:938
Página de fin:952.e6
DOI: http://dx.doi.org/10.1016/j.molcel.2018.02.018
Título revista:Molecular Cell
Título revista abreviado:Mol. Cell
ISSN:10972765
CODEN:MOCEF
CAS:cyclin dependent kinase, 150428-23-2; mitogen activated protein kinase, 142243-02-5; Adaptor Proteins, Signal Transducing; CLN1 protein, S cerevisiae; CLN2 protein, S cerevisiae; Cyclin-Dependent Kinases; Cyclins; FUS3 protein, S cerevisiae; Mitogen-Activated Protein Kinases; Saccharomyces cerevisiae Proteins; STE5 protein, S cerevisiae
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10972765_v69_n6_p938_Repetto

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Citas:

---------- APA ----------
Repetto, M.V., Winters, M.J., Bush, A., Reiter, W., Hollenstein, D.M., Ammerer, G., Pryciak, P.M.,..., Colman-Lerner, A. (2018) . CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5. Molecular Cell, 69(6), 938-952.e6.
http://dx.doi.org/10.1016/j.molcel.2018.02.018
---------- CHICAGO ----------
Repetto, M.V., Winters, M.J., Bush, A., Reiter, W., Hollenstein, D.M., Ammerer, G., et al. "CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5" . Molecular Cell 69, no. 6 (2018) : 938-952.e6.
http://dx.doi.org/10.1016/j.molcel.2018.02.018
---------- MLA ----------
Repetto, M.V., Winters, M.J., Bush, A., Reiter, W., Hollenstein, D.M., Ammerer, G., et al. "CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5" . Molecular Cell, vol. 69, no. 6, 2018, pp. 938-952.e6.
http://dx.doi.org/10.1016/j.molcel.2018.02.018
---------- VANCOUVER ----------
Repetto, M.V., Winters, M.J., Bush, A., Reiter, W., Hollenstein, D.M., Ammerer, G., et al. CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5. Mol. Cell. 2018;69(6):938-952.e6.
http://dx.doi.org/10.1016/j.molcel.2018.02.018