Year: 2012
Type: book-chapter
Abstract: The mitogen activated protein kinase (MAPK) cascade is a family of serine-threonine protein kinases controlling a vast array of cellular responses.Among the oldest signaling pathways known, the MAPK cascade is evolutionarily conserved, being found in species ranging from yeast to humans (Widmann et al., 1999).All eukaryotic cells possess multiple MAPK signaling pathways.In mammals, four major subfamilies (termed classical MAPKs) have been identified including extracellular signal-regulated kinase 1/2 (ERK1/2), c-jun Nterminal protein kinases (JNK/SAPK), p38 isoforms (p38 , , , or ), and ERK5 (Dhanasekaran and Johnson, 2007).These multiple parallel MAPK cascades all operate through a three tiered system characterized by consecutive phosphorylation events.Each of the pathways is equipped to respond to a remarkably diverse array of stimuli, including cytokines, growth factors, irradiation, hormones, injury, and stress (Cargnello and Roux, 2011).The binding of stimuli to receptors triggers the initial phosphorylation events.These events transform inactive MAP3K into active MAP3K.Subsequently, active MAP3K phosphorylates, and thereby activates, downstream MAP2K (MEK) proteins.The active MAP2K proteins then phosphorylate MAPK (ERK) molecules.These MAPK proteins then regulate the transcription of a diverse group of genes involved in inflammation, cell survival, cell division, development, metabolism, differentiation, motility, and repair (Cargnello and Roux, 2011).Additionally, over the last two decades atypical pathways including ERK 3/4, ERK 7/8 and Nemo-like kinase (NLK) have been discovered (Cargnello and Roux, 2011).Similar to classical MAPK family members, these proteins phosphorylate target substrates on serine or threonine residues.However, they are not organized into the classical three-tiered model and contain a less well conserved motif on the activation loop of the kinase domain.Due to the diverse effects that MAPK signaling pathways have on cellular processes, the classical MAPK pathways have been intensely studied to assess their role in human disease.Detailed reviews for each pathway were previously published (Weston and Davis, 2007;
Source: InTech eBooks
DOI: 10.5772/38135
Authors: Katie DeCicco-Skinner, Monika Deshpande, Jonathan Wiest
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W1503700547