scholarly journals Mechanisms of MAPK signalling specificity

2006 ◽  
Vol 34 (5) ◽  
pp. 837-841 ◽  
Author(s):  
L. Bardwell
Keyword(s):  
Cellular Response ◽  
Short Review ◽  
Feedback Loops ◽  
Scaffold Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Regulatory Circuits ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Protein Kinase Signalling

MAPK (mitogen-activated protein kinase) signalling pathways contribute to the regulation of diverse responses, including normal and pathological aspects of cell growth, division, differentiation and death. Their ubiquity and versatility raise the issue of how they achieve specific coupling of signal with cellular response. How do the kinases in the cascade distinguish their correct substrates from the vast excess of incorrect substrates? Furthermore, how do different signals elicit distinct responses when they are transmitted by the same components? This short review highlights several mechanisms that can promote specificity in MAPK signalling, including tethering interactions between MAPKs and their substrates and regulators mediated by docking sites, feedback loops and cross-pathway regulatory circuits, and the selective activation of scaffold proteins.

The JIP family of MAPK scaffold proteins

2006 ◽  
Vol 34 (5) ◽  
pp. 828-832 ◽  
Author(s):  
A.J. Whitmarsh
Keyword(s):  
Cell Function ◽  
Biochemical Properties ◽  
Scaffold Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Signal Integration ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Β Cell Function ◽  
Insulin Responses ◽  
Protein Kinase Signalling

The components of MAPK (mitogen-activated protein kinase) signalling pathways can assemble into complexes that are co-ordinated by regulatory proteins including scaffold proteins. There is increasing evidence that scaffold proteins (i) maintain signalling specificity and facilitate the activation of pathway components, (ii) localize pathway components to particular subcellular sites or to specific targets, and (iii) serve as a point of signal integration to allow regulation of MAPK pathways by other signalling events in the cell. One family of scaffold proteins that regulate signalling by stress-activated MAPKs are the JIPs [JNK (c-Jun N-terminal kinase)-interacting proteins]. JIP proteins have been demonstrated to form complexes with specific JNK and p38 MAPK signalling modules and to play important roles in brain development, neuronal trafficking, apoptosis, β-cell function and insulin responses. Here, I briefly review our current understanding of the biochemical properties and physiological roles of JIP proteins.

Mechanisms and functions of p38 MAPK signalling

2010 ◽  
Vol 429 (3) ◽  
pp. 403-417 ◽  
Author(s):  
Ana Cuadrado ◽  
Angel R. Nebreda
Keyword(s):  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Mitogen Activated Protein Kinase ◽  
Wide Range ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
External Signals ◽  
Protein Kinase Signalling ◽  
Genetic Mouse Models

The p38 MAPK (mitogen-activated protein kinase) signalling pathway allows cells to interpret a wide range of external signals and respond appropriately by generating a plethora of different biological effects. The diversity and specificity in cellular outcomes is achieved with an apparently simple linear architecture of the pathway, consisting of a core of three protein kinases acting sequentially. In the present review, we dissect the molecular mechanisms underlying p38 MAPK functions, with special emphasis on the activation and regulation of the core kinases, the interplay with other signalling pathways and the nature of p38 MAPK substrates as a source of functional diversity. Finally, we discuss how genetic mouse models are facilitating the identification of physiological functions for p38 MAPKs, which may impinge on their eventual use as therapeutic targets.

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