Related Experiment Video
Updated: May 13, 2026
07:55
Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment
Published on: September 25, 2017
Mitogen-Activated Protein (MAP) Kinase Scaffolding Proteins: A Recount
Melanie Meister1, Ana Tomasovic, Antje Banning
1Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany. ritva.tikkanen@biochemie.med.uni-giessen.de.
International Journal of Molecular Sciences
|March 5, 2013
Summary
Mitogen-activated protein kinase (MAPK) pathway signaling is fine-tuned by scaffolding proteins, which coordinate cellular responses. This review highlights recent advances in understanding MAPK/extracellular signal-regulated kinase (ERK) pathway scaffolders, including novel and lesser-known members.
Area of Science:
- Cellular signaling
- Molecular biology
- Biochemistry
Background:
- The mitogen-activated protein kinase (MAPK) pathway, including the extracellular signal-regulated kinase (ERK) cascade, is crucial for cellular processes regulated by receptor tyrosine kinases.
- Signal strength and duration dictate cellular outcomes, such as proliferation versus differentiation, within the MAPK pathway.
- MAPK signaling is modulated by scaffolding proteins that bind multiple pathway components, influencing signal transduction and cellular responses.
Purpose of the Study:
- To review recent advancements in the study of MAPK/ERK pathway scaffolders.
- To focus on both well-established and newly identified MAPK scaffolding proteins.
- To elucidate the role of scaffolders in coordinating complex cellular signaling events.
Main Methods:
- Literature review of recent research on MAPK/ERK pathway scaffolders.
- Synthesis of information on known scaffolders like Kinase Suppressor of Ras (KSR).
- Emphasis on the functional roles of recently identified scaffolders, including fibroblast growth factor receptor substrate 2, flotillin-1, and mitogen-activated protein kinase organizer 1.
Main Results:
- Scaffolding proteins are critical regulators of MAPK/ERK pathway signaling specificity and efficiency.
- Well-characterized scaffolders like KSR play significant roles in signal transduction.
- Emerging scaffolders such as FRS2, flotillin-1, and MINT1 are increasingly recognized for their contributions to MAPK pathway regulation.
Conclusions:
- MAPK scaffolding proteins are essential for precise control of cellular signaling.
- Understanding these scaffolders provides insights into diverse cellular functions and potential therapeutic targets.
- Further research into less-studied scaffolders will deepen our comprehension of MAPK pathway dynamics.
Related Concept Videos
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:42Microtubule Associated Proteins (MAPs)
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...