MAPK scaffold proteins are dynamic entities that (i) directly interact with multiple components of the MAPK signaling complex, (ii) consolidate or sequester protein interactions to physically insulate the MAPK pathway to specific cellular locations as well as (iii) regulate signal strength and stimulus-specific responses to efficiently transmit MAPK signals in a spatiotemporal manner and narrow its actions ( Brown and Sacks, 2009). Studies have suggested that scaffolding proteins are emerging as playing an essential role in regulating the MAPK signaling response ( Brown and Sacks, 2009). How this single pathway regulates diverse functions and achieves specificity in function in different cell types has been a longstanding question in the field.
The mitogen activated protein kinase (MAPK)/extracellular regulated kinase (ERK) signaling pathway is one of the first blueprints describing how extracellular cues/factors (growth factors and hormones) generate intracellular signals and converge on the nucleus to drive gene expression and a wide range of cellular functions ( Pearson et al., 2001). Scaffold Proteins That Regulate Erk-Associated Mitogen Activated Protein Kinase Function: Growing Importance In Cardiac Hypertrophy In this review, we provide insights on ERK-associated scaffolding proteins regulating cardiac myofilament function and their impact on cardiac hypertrophy and disease. Emerging data has uncovered specific MAPK scaffolding proteins that tether MAPK/ERK signaling specifically at the sarcomere and plasma membrane in cardiac muscle and show that deficiencies in these scaffolding proteins alter ERK activity and phosphorylation, which are then critical in altering the cardiac myocyte response to stress-induced hypertrophy and disease progression. However, more recent studies have highlighted that these signaling pathways may exert their regulatory functions in a more compartmentalized manner in cardiac muscle. Studies in genetic mouse models deficient in ERK-associated MAPK components pathway have further reinforced a direct role for this pathway in stress-induced cardiac hypertrophy and disease.
The mitogen activated protein kinase (MAPK)-extracellular regulated kinase 1/2 (ERK1/2) pathway is a central downstream signaling pathway that is activated in cardiac muscle cells during mechanical and agonist-mediated hypertrophy.
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