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Biomolecules
Special Issues
MAP Kinases: Functions in Signal Transduction and Disease
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MAP Kinases: Functions in Signal Transduction and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Enzymology".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 9172

Special Issue Editor

Prof. Dr. Piero Crespo

E-Mail Website
Guest Editor
CSIC Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Santander, Spain
Interests: Ras-ERK pathway spatial regulation; scaffold proteins; protein-protein interactions as therapeutic targets
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since their discovery in the early 1990s, our knowledge on MAP kinases has expanded exponentially; as a result, they have been afforded a prominent position as essential mediators in signaling cascades that regulate key cellular events, and as prime participants in the onset and progression of an ample panel of maladies.

This Special Issue of Biomolecules explores the most recent advances in our understanding of mechanisms whereby MAP kinases transduce extracellular cues to convert them into specific cellular outputs, the pathological consequences of MAP kinases signaling going awry, and how MAP kinase cascades are emerging as potential therapeutic targets for the treatment of a broad spectrum of diseases.

Prof. Dr. Piero Crespo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • MAP kinase
  • ERK
  • JNK
  • p38
  • scaffold proteins

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Published Papers (2 papers)

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Research

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19 pages, 2480 KiB  
Article
A Combination of Conformation-Specific RAF Inhibitors Overcome Drug Resistance Brought about by RAF Overexpression
by Hiroaki Imoto, Nora Rauch, Ashish J. Neve, Fahimeh Khorsand, Martina Kreileder, Leonidas G. Alexopoulos, Jens Rauch, Mariko Okada, Boris N. Kholodenko and Oleksii S. Rukhlenko
Biomolecules 2023, 13(8), 1212; https://doi.org/10.3390/biom13081212 - 2 Aug 2023
Cited by 2 | Viewed by 3040
Abstract
Cancer cells often adapt to targeted therapies, yet the molecular mechanisms underlying adaptive resistance remain only partially understood. Here, we explore a mechanism of RAS/RAF/MEK/ERK (MAPK) pathway reactivation through the upregulation of RAF isoform (RAFs) abundance. Using computational modeling and in vitro experiments, [...] Read more.
Cancer cells often adapt to targeted therapies, yet the molecular mechanisms underlying adaptive resistance remain only partially understood. Here, we explore a mechanism of RAS/RAF/MEK/ERK (MAPK) pathway reactivation through the upregulation of RAF isoform (RAFs) abundance. Using computational modeling and in vitro experiments, we show that the upregulation of RAFs changes the concentration range of paradoxical pathway activation upon treatment with conformation-specific RAF inhibitors. Additionally, our data indicate that the signaling output upon loss or downregulation of one RAF isoform can be compensated by overexpression of other RAF isoforms. We furthermore demonstrate that, while single RAF inhibitors cannot efficiently inhibit ERK reactivation caused by RAF overexpression, a combination of two structurally distinct RAF inhibitors synergizes to robustly suppress pathway reactivation. Full article
(This article belongs to the Special Issue MAP Kinases: Functions in Signal Transduction and Disease)
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Review

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48 pages, 2654 KiB  
Review
Navigating the ERK1/2 MAPK Cascade
by Ana Martin-Vega and Melanie H. Cobb
Biomolecules 2023, 13(10), 1555; https://doi.org/10.3390/biom13101555 - 20 Oct 2023
Cited by 26 | Viewed by 5365
Abstract
The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological processes including proliferation, cell cycle control, growth, and survival; common across all cell types. Notably, ERK1/2 are implicated in specific processes in a context-dependent manner as in stem cells and pancreatic [...] Read more.
The RAS-ERK pathway is a fundamental signaling cascade crucial for many biological processes including proliferation, cell cycle control, growth, and survival; common across all cell types. Notably, ERK1/2 are implicated in specific processes in a context-dependent manner as in stem cells and pancreatic β-cells. Alterations in the different components of this cascade result in dysregulation of the effector kinases ERK1/2 which communicate with hundreds of substrates. Aberrant activation of the pathway contributes to a range of disorders, including cancer. This review provides an overview of the structure, activation, regulation, and mutational frequency of the different tiers of the cascade; with a particular focus on ERK1/2. We highlight the importance of scaffold proteins that contribute to kinase localization and coordinate interaction dynamics of the kinases with substrates, activators, and inhibitors. Additionally, we explore innovative therapeutic approaches emphasizing promising avenues in this field. Full article
(This article belongs to the Special Issue MAP Kinases: Functions in Signal Transduction and Disease)
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