cGKI Substrates

Bcl-2 (Ser 70) plays a pivotal role in apoptosis regulation by modulating mitochondrial membrane permeability. Phosphorylation at this serine residue enhances its anti-apoptotic function, stabilizing the protein's conformation and promoting interactions with pro-apoptotic factors. This modification influences the release of cytochrome c, thereby impacting the intrinsic apoptotic pathway. The kinetics of these interactions are crucial for cellular survival and stress responses.

γPAK (Thr 402) acts as a critical modulator in cellular signaling pathways, particularly influencing protein-protein interactions through its unique phosphorylation state. This modification alters the conformational dynamics of target proteins, enhancing their affinity for specific binding partners. The resulting changes in molecular interactions can significantly affect downstream signaling cascades, impacting cellular responses to environmental stimuli. Its role in regulating these pathways underscores its importance in maintaining cellular homeostasis.

GluR1 (Ser 863) serves as a pivotal component in synaptic transmission, particularly through its phosphorylation status, which modulates receptor activity. This modification influences the receptor's ion channel properties, enhancing its permeability to cations. The dynamic interplay between GluR1 and associated scaffolding proteins facilitates the clustering of receptors at synapses, thereby optimizing neurotransmission efficiency. Its regulatory role in excitatory signaling pathways is crucial for synaptic plasticity.

NOS3 (Thr 495) is integral to nitric oxide synthesis, where its phosphorylation state significantly influences enzyme activity and substrate affinity. This modification enhances the enzyme's interaction with calmodulin, promoting a conformational change that optimizes electron transfer during the catalytic cycle. The resulting nitric oxide plays a critical role in various signaling pathways, affecting vascular tone and cellular communication. Its kinetic properties are essential for rapid response in physiological processes.

WT (Ser 393) functions as a key regulator in lipid metabolism, exhibiting unique interactions with acyl-CoA derivatives. Its phosphorylation alters the enzyme's conformation, enhancing substrate binding and facilitating the transfer of acyl groups. This modification influences reaction kinetics, promoting efficient catalysis in fatty acid synthesis. Additionally, WT's ability to interact with specific lipid membranes underscores its role in cellular signaling and metabolic pathways, contributing to homeostasis.

Adducin (Ser 662) plays a pivotal role in cytoskeletal dynamics, particularly in the assembly and stabilization of actin filaments. Its phosphorylation state modulates interactions with spectrin and other cytoskeletal proteins, influencing cellular shape and motility. This modification also affects the binding affinity for membrane components, thereby impacting signal transduction pathways. The kinetics of these interactions are crucial for maintaining cellular integrity and facilitating rapid responses to environmental changes.

Na+/K+-ATPase α (Ser 943) is integral to ion transport across cellular membranes, specifically regulating sodium and potassium gradients. Its phosphorylation at Ser 943 enhances enzyme activity, influencing ATP hydrolysis rates and ion exchange kinetics. This modification alters conformational states, facilitating the transition between inward and outward-facing forms. The enzyme's interactions with lipid bilayers and associated proteins are critical for maintaining electrochemical gradients essential for cellular excitability and signaling.

IRS-1 (Ser 270) plays a pivotal role in cellular signaling pathways, particularly in the insulin signaling cascade. Phosphorylation at Ser 270 modulates its interaction with downstream effectors, influencing metabolic processes. This modification enhances IRS-1's binding affinity to specific SH2 domain-containing proteins, promoting the activation of PI3K and MAPK pathways. The dynamic conformational changes induced by phosphorylation facilitate critical protein-protein interactions, impacting cellular growth and glucose homeostasis.

p21 Waf1/Cip1 (Ser 146) is a crucial regulator of the cell cycle, particularly in response to stress signals. Phosphorylation at Ser 146 enhances its stability and promotes interactions with cyclin-dependent kinases, effectively inhibiting their activity. This modification triggers a cascade of downstream effects, leading to cell cycle arrest. The unique conformational changes induced by this phosphorylation facilitate its role in tumor suppression and cellular senescence, impacting overall cellular proliferation.