Scaffold coupling: ERK activation by trans-phosphorylation across different scaffold protein species
| Autor: | Ana Martín-Vega, Laura Ruiz-Peinado, Rocío García-Gómez, Ana Herrero, Dalia de la Fuente-Vivas, Swetha Parvathaneni, Rubén Caloto, Marta Morante, Alex von Kriegsheim, Xosé R. Bustelo, David B. Sacks, Berta Casar, Piero Crespo |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Martín-Vega, A, Ruiz-Peinado, L, García-Gómez, R, Herrero, A, de la Fuente-Vivas, D, Parvathaneni, S, Caloto, R, Morante, M, von Kriegsheim, A, R Bustelo, X, B Sacks, D, Casar, B & Crespo, P 2023, ' Scaffold coupling: ERK activation by trans-phosphorylation across different scaffold protein species. ', Science Advances . https://doi.org/10.1126/sciadv.add7969 |
| DOI: | 10.1126/sciadv.add7969 |
| Popis: | Resumen del trabajo presentado en el II Congreso Anual de la Red Conexión Cáncer, celebrado en Alicante (España) del 23 al 25 de enero de 2023. ERK 1/2 proteregulatory proteins like scaffold proteins, that link the components of MAP kinases sequential tiers to form a multienzymatic complex. This way ERK signals are fine-tune (amplitude, intensity and duration), afford signal fidelity and have spatial selectivity. Some examples of scaffold proteins are KSR1, that bind C/BRAF, MEK1/2 and ERK1/2, and IQGAP1, that binds BRAF, MEK1/2 AND ERK1/2. In both cases depletion or blockade of this scaffold functions prevents RAS-ERK pathway-driven neoplasia. We demostrated that ERK can binds constitutively to scaffold, to be cis-phosphorylated therein by scaffold-bound MEK which would enable its binding to a free, phosphorylated ERK monomer to form a dimer. We have found that KSR1 y IQGAP1 can functionally associate with each other. As a consecuence, ERK docked at KSR1 can be phosphorylated by MEK bound to IQGAP1, a process named ¿trans-phosphorylarion¿. The results identify interactions betweeen scaffold proteins as a higher-order level of regulation in the ERK cascade. ins are major actors in the transduction of signals conveyed by external stimuli to the interior of the cell, being regulators of biochemical processes such as proliferation, differentiation or survival. ERK signals are modulated by different |
| Databáze: | OpenAIRE |
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