Taiy Chemical
(Ala286)-Calmodulin-Dependent Protein Kinase II
Synonym CAMK2A
Species Human
Protein Accession P11277
Purity ≥95%
Endotoxin Level <1.0 EU per μg protein
Biological Activity Not specified
Expression System Insect Cells
Fusion Tag His Tag
Predicted Molecular Mass 53.2 kDa
Formulation Liquid in 25 mM Tris-HCl buffer
Reconstitution No reconstitution needed. Simply thaw and use.
Storage & Stability Store at -80°C. For long term storage, store at -80°C or -20°C.
FAQ
How does (Ala286)-Calmodulin-Dependent Protein Kinase II contribute to cellular signal transduction, and why is it significant?

(Ala286)-Calmodulin-Dependent Protein Kinase II, specifically characterizes a modified version of the enzyme that plays a pivotal role in cellular signal transduction. Calmodulin-Dependent Protein Kinase II (CaMKII) is a multifunctional enzyme, essential in translating calcium signals, which are ubiquitous in many cellular processes. Calcium ions act as a universal signaling molecule, responding to various external stimuli and modulating numerous intracellular pathways. CaMKII becomes activated upon binding to the calcium/calmodulin complex, which is indicative of elevated intracellular calcium levels.

The significance of CaMKII, and particularly its variant (Ala286), lies in its ability to phosphorylate a multitude of substrates within the cell, influencing numerous physiological processes. The Ala286 mutation influences the enzyme's autophosphorylation capability, which is critical for sustaining its activity even after the calcium signal diminishes. This feature is particularly crucial in the context of neuronal functions where it impacts synaptic plasticity – a fundamental mechanism underlying learning and memory. When activated, CaMKII can phosphorylate synaptic proteins, leading to modifications in their structure and function, thus affecting the strength and efficacy of synapses. Such synaptic alterations are essential for processes like Long-Term Potentiation (LTP), which is a long-lasting increase in synaptic strength following high-frequency stimulation.

Research into (Ala286)-CaMKII continues to unravel its contributions to neuronal plasticity and its potential role in neurodegenerative diseases. Moreover, given that dysregulation of calcium-dependent signaling pathways is implicated in a variety of pathological conditions, understanding the specific roles and regulatory mechanisms of CaMKII can illuminate pathways for therapeutic interventions. Beyond the nervous system, CaMKII is involved in other vital processes including cardiac function, where it influences heart muscle contraction and rhythmicity by modulating ion channel activity. Its ubiquitous presence across different tissues underscores the enzyme’s broad biological significance, making it a crucial element in the study of cellular signaling dynamics and a potential target for modulating responses in diseases characterized by aberrant calcium signaling.

What research developments have there been recently concerning (Ala286)-Calmodulin-Dependent Protein Kinase II?

Recently, advancements in the study of (Ala286)-Calmodulin-Dependent Protein Kinase II have expanded significantly, primarily driven by the integration of cutting-edge techniques in structural biology, genomics, and neurosciences. Studies have increasingly focused on elucidating the structural intricacies of the Ala286 mutation to gain deeper insights into the functional enhancements attributed to this form of CaMKII. Using cryo-electron microscopy and X-ray crystallography, researchers have been able to visualize the three-dimensional conformational changes in (Ala286)-CaMKII, delineating the specific mechanistic pathways it engages in upon autophosphorylation. This structural insight is essential as it informs the biochemical basis of its prolonged activity, even in the absence of calcium/calmodulin binding.

Moreover, genomic studies have leveraged CRISPR-Cas9 technology to create mutant strains and cell lines that express the Ala286 variant of CaMKII to observe the resultant physiological and behavioral changes. These models have been instrumental in exploring the role of (Ala286)-CaMKII in memory retention and cognitive flexibility in animal models, thereby enhancing our understanding of its impact on learning processes. Additionally, these genetic models have helped delineate how aberrations in this kinase might contribute to neurodegenerative conditions and cognitive disorders, offering potential therapeutic targets.

In neuroscience, the application of optogenetics and advanced in vivo imaging techniques has revealed how (Ala286)-CaMKII modulates synaptic activity and neuronal circuits in real-time. Such studies have highlighted its essential role in synapsis-specific plasticity and how it orchestrates complex behaviors through the modulation of synaptic strength over time. Furthermore, in the context of cardiac research, there has been a concerted effort to study the role of (Ala286)-CaMKII in cardiac hypertrophy and heart failure, aiming to differentiate its beneficial and maladaptive roles in heart tissue remodeling and calcium handling.

Collectively, these research developments underline the broadened scope of knowledge regarding (Ala286)-CaMKII and establish a foundation for future exploration into therapeutic approaches that can harness its activity to treat conditions marked by calcium dysregulation. The interplay of different methodologies and collaborative research networks has thus significantly propelled the understanding of this nuanced kinase and its role within broader physiological contexts.

What are the challenges associated with targeting (Ala286)-Calmodulin-Dependent Protein Kinase II in therapeutic treatments?

Targeting (Ala286)-Calmodulin-Dependent Protein Kinase II in therapeutic treatments presents several challenges, stemming from the complexity of its biological roles and the delicate balance of its signaling activities. One of the primary challenges lies in achieving specificity in targeting (Ala286)-CaMKII without adversely affecting other isoforms of CaMKII that perform distinct and essential functions in various tissues. The kinase's ubiquitous expression across different organ systems implies that any therapeutic intervention must precisely discern its beneficial functions from its pathogenic roles.

Another challenge is related to the autophosphorylation activity of (Ala286)-CaMKII, which can perpetuate its activity even in the absence of calcium, making it difficult to regulate once activated. This persistent activity necessitates designing therapeutic agents that can either selectively inhibit the hyperactive state of the kinase or promote its dephosphorylation, restoring normal regulatory control without disrupting regular cellular calcium signaling, which is vital for numerous physiological processes.

The structural conformations of (Ala286)-CaMKII add another layer of complexity, as interventions that affect its structure could lead to unforeseen consequences on its interaction with a wide array of substrates and binding partners. Additionally, the transient and localized nature of calcium-dependent signaling that involves CaMKII complicates the ability to target its activity with precision, maintaining local signaling specificity while avoiding systemic side effects.

Furthermore, consideration must be given to the compensatory pathways that might be activated when (Ala286)-CaMKII is inhibited. Inhibition could potentially lead to upregulation or downregulation of other kinases and pathways, altering cellular homeostasis and triggering undesired side effects. This necessitates a comprehensive understanding of the kinase's role in cellular networks to anticipate and mitigate any compensatory mechanisms that might compromise therapeutic efficacy.

Clinical translation of research targeting (Ala286)-CaMKII also faces hurdles in the form of delivery systems. Developing drug delivery methods that ensure adequate bioavailability, penetrance, and retention in target tissues without eliciting off-target actions presents an additional challenge. Moreover, inter-individual variability in genetic make-up and disease pathology requires personalized approaches to ensure that therapeutic targeting of (Ala286)-CaMKII is both safe and effective across different patient populations.

In summary, while the therapeutic targeting of (Ala286)-CaMKII offers potential benefits in conditions characterized by aberrant calcium signaling, it is fraught with challenges that necessitate carefully designed strategies to harness its mechanisms without disrupting critical cellular functions. Continued research into its regulation, structural dynamics, and involvement in broader signaling pathways is essential to overcome these challenges.

How does (Ala286)-Calmodulin-Dependent Protein Kinase II influence learning and memory processes?

(Ala286)-Calmodulin-Dependent Protein Kinase II (CaMKII) plays an influential role in learning and memory processes through its critical involvement in synaptic plasticity, which is the cellular mechanism underlying these cognitive functions. Synaptic plasticity refers to the ability of synapses, the communication junctions between neurons, to strengthen or weaken over time in response to increases or decreases in activity. CaMKII, particularly in its (Ala286) variant, is essential for initiating and maintaining these modifications, thereby facilitating the encoding and storage of information in neural circuits.

The activation of (Ala286)-CaMKII is triggered by the binding of calcium-bound calmodulin, which occurs when there is an influx of calcium ions into the neuron following synaptic activation. Upon activation, (Ala286)-CaMKII undergoes autophosphorylation, a self-modification that substantially prolongs its active state, allowing it to sustain activity even in the absence of continuous calcium signals. This prolonged activity plays a pivotal role in the induction and maintenance of long-term potentiation (LTP), a persistent strengthening of synapses that is widely recognized as a foundational mechanism for memory formation and learning.

(Ala286)-CaMKII influences learning and memory by modifying the properties of synaptic receptors. For instance, one of its key functions is the regulation of AMPA-type glutamate receptors at the synapse, which determines the synaptic response to glutamate, a major excitatory neurotransmitter in the brain. By phosphorylating these receptors, (Ala286)-CaMKII enhances their conductance, thereby increasing synaptic strength and facilitating the LTP process.

Moreover, (Ala286)-CaMKII's ability to bind to specific sites within the synaptic architecture allows it to scaffold additional signaling molecules, orchestrating a multi-layered signaling complex that crucially influences the structural components of the postsynaptic density. This role is instrumental in initiating structural changes that support synaptic scaling and remodeling, critical aspects of learning and memory.

Additionally, (Ala286)-CaMKII serves as a molecular memory switch. Its autophosphorylation confers the ability to retain a 'memory' of past calcium signals, enabling neurons to adapt to new inputs based on previous experiences. This property underscores its status not only as a signaling molecule but also as a molecular integrator of past and present signals, thus playing a strategic role in both the short-term and long-term memory consolidation.

Further research delves into the specific contributions of (Ala286)-CaMKII in the pathophysiology of memory-related disorders, highlighting its potential as a therapeutic target to ameliorate cognitive impairments. Its central role in synaptic plasticity and the dynamic regulation of neural connectivity makes it an invaluable focus of study in the quest to understand and harness the cognitive capabilities of the human brain.

What are the physiological roles of (Ala286)-Calmodulin-Dependent Protein Kinase II beyond the nervous system?

Beyond its well-documented role in the nervous system, (Ala286)-Calmodulin-Dependent Protein Kinase II (CaMKII) performs a myriad of physiological functions across different body systems, underlining its versatility as a key regulatory enzyme. Its widespread presence and functional implications showcase the kinase's involvement in various cellular processes and biological contexts outside the neuronal milieu.

One of the primary roles of (Ala286)-CaMKII beyond the nervous system is in the cardiovascular field. It is instrumental in regulating heart muscle contraction and cardiac rhythm through its action on calcium channels and other cardiac proteins. Specifically, it modulates the activity of sarcoplasmic reticulum calcium release channels, which are critical for the excitation-contraction coupling in cardiac myocytes. By influencing calcium cycling within these cells, (Ala286)-CaMKII plays a significant role in both cardiac contractility and arrhythmogenesis. This dual role makes it a critical factor in the physiological adaptation of heart muscle to various stressors and pathological conditions such as heart failure and hypertrophy.

In skeletal muscle, (Ala286)-CaMKII contributes to the regulation of muscle contraction and metabolism by modulating calcium signaling pathways involved in muscle fiber adaptation to exercise. It affects mitochondrial biogenesis and influences aerobic metabolism, thereby contributing to overall muscular endurance and performance. Additionally, it has a role in the regulation of glucose uptake in response to insulin, implicating it in energy homeostasis and metabolic health.

In the immune system, (Ala286)-CaMKII facilitates the activation and differentiation processes of lymphocytes. It participates in the signaling cascades triggered by antigen receptor engagement on immune cells, thereby aiding in adaptive immune responses. Its involvement in these pathways exemplifies its function in the immune surveillance mechanisms and response regulation, making it relevant in the context of immune disorders and inflammation.

Furthermore, (Ala286)-CaMKII is involved in the regulation of gene expression through transcriptional modulation in several cell types. By participating in the regulation of signaling pathways that control nuclear factor activity, (Ala286)-CaMKII contributes to gene expression patterns that determine cellular responses to therapeutic agents and environmental stressors, influencing processes such as cell growth, differentiation, and apoptosis.

In conclusion, the roles of (Ala286)-CaMKII extend well beyond neuronal signal transduction, impacting various functional aspects in cardiovascular physiology, muscle metabolism, immune function, and gene regulation. Its multifunctional nature and systemic relevance continue to be a central focus of research, holding promise for therapeutic insights not only in neurobiology but in broader biomedical contexts where calcium-dependent signaling is pivotal.
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