Artículo
CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5
Repetto, María Victoria
; Winters, Matthew J.; Bush, Alan
; Reiter, Wolfgang; Hollenstein, David Maria; Ammerer, Gustav; Pryciak, Peter M.; Colman Lerner, Alejandro Ariel
Fecha de publicación:
03/2018
Editorial:
Cell Press
Revista:
Molecular Cell
ISSN:
1097-2765
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
CDC28
,
CKS1
,
CLN2
,
CYCLIN
,
G PROTEIN
,
MATING
,
PHEROMONE
,
SIGNAL TRANSDUCTION
,
START
,
STE4
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Colecciones
Articulos(IFIBA)
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Citación
Repetto, María Victoria; Winters, Matthew J.; Bush, Alan; Reiter, Wolfgang; Hollenstein, David Maria; et al.; CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5; Cell Press; Molecular Cell; 69; 6; 3-2018; 938-952.e6
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