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Akt Pathway

Akt Pathway Background

About Akt Pathway

The Akt pathway, also known as the PI3K-Akt pathway, is a highly conserved cellular signaling pathway that plays a crucial role in regulating various cellular processes such as cell growth, proliferation, survival, metabolism, and angiogenesis. It is activated in response to various extracellular signals, including growth factors, cytokines, hormones, and other stimuli.

The Akt pathway starts with the activation of phosphatidylinositol 3-kinase (PI3K) enzyme, which converts phosphatidylinositol-4,5-bisphosphate (PIP2) into phosphatidylinositol-3,4,5-trisphosphate (PIP3). PIP3 serves as a docking site for Akt, also known as protein kinase B (PKB), which is translocated to the plasma membrane.

Once on the plasma membrane, Akt is phosphorylated at two critical sites, Thr308 and Ser473, by phosphoinositide-dependent kinase 1 (PDK1) and mammalian target of rapamycin complex 2 (mTORC2), respectively. The phosphorylation of Akt at these sites leads to its full activation and subsequent translocation into the cytoplasm and nucleus.

Activated Akt phosphorylates a wide range of downstream targets, including proteins involved in cell survival (such as BAD and FOXO), protein synthesis (such as mTOR and glycogen synthase kinase-3), and metabolism (such as glucose transporter GLUT4). This phosphorylation event promotes cell growth, inhibits apoptosis, promotes protein synthesis, and regulates glucose metabolism.

Furthermore, the Akt pathway can also activate several signaling cascades, such as the mitogen-activated protein kinase (MAPK) pathway, which further enhances its impact on cellular processes.

Dysregulation of the Akt pathway has been implicated in various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the Akt pathway and its associated signaling events is crucial in developing targeted therapies for these diseases.

In conclusion, the Akt pathway is a critical signaling pathway involved in regulating various cellular processes. Its dysregulation can contribute to the development and progression of numerous diseases, including cancer, metabolic disorders, and neurodegenerative diseases. Activation of the Akt pathway promotes cell survival, growth, and proliferation, while inhibition leads to cell cycle arrest and apoptosis. Therefore, understanding the mechanisms and regulation of the Akt pathway is crucial for developing targeted therapies and improving disease management. Ongoing research continues to uncover the intricate workings of this pathway and its potential as a therapeutic target.

Akt Pathway - Creative BioMart

Multiple Components and Molecules in Akt Pathway

The Akt pathway involves multiple components and molecules that work together to regulate various cellular processes. These include adaptor proteins, intracellular kinases, phosphatases, phospholipases, small GTPases, receptor tyrosine kinases (RTKs), transcription factors, translation regulation-related molecules, and ubiquitin-related molecules.

Adaptor proteins play a crucial role in linking extracellular signals to intracellular signaling pathways. They mediate the recruitment and activation of downstream signaling molecules. Examples of adaptor proteins in the Akt pathway include IRS (insulin receptor substrate) proteins and GRB2 (growth factor receptor-bound protein 2).

Intracellular kinases , such as PI3K (phosphatidylinositol 3-kinase), are key components of the Akt pathway. They phosphorylate the inositol phospholipids in the cell membrane, generating the lipid second messenger PIP3 (phosphatidylinositol (3,4,5)-trisphosphate). PIP3 serves as a docking site for Akt and helps to recruit it to the plasma membrane.

Phosphatases , on the other hand, deactivate the Akt pathway by dephosphorylating key molecules. PTEN (phosphatase and tensin homolog) is a well-known phosphatase that negatively regulates the Akt pathway by dephosphorylating PIP3.

Phospholipases, small GTPases, and other molecules also play roles in the Akt pathway by regulating various signaling events. For example, phospholipase C (PLC) cleaves PIP2 (phosphatidylinositol (4,5)-bisphosphate) into IP3 (inositol trisphosphate) and DAG (diacylglycerol), which further activate downstream signaling molecules.

Receptor tyrosine kinases (RTKs) play a central role in initiating the Akt pathway. These transmembrane proteins span the plasma membrane and possess an extracellular ligand-binding domain, a transmembrane domain, and an intracellular catalytic tyrosine kinase domain. The binding of specific ligands to RTKs triggers their dimerization and autophosphorylation of tyrosine residues. This allows them to serve as docking sites for adaptor proteins, such as the p85 subunit of PI3K.

Transcription factors act downstream of Akt activation to regulate gene expression. The Akt pathway activates several transcription factors, including nuclear factor κB (NF-κB), Forkhead box O (FOXO) proteins, and mammalian target of rapamycin complex 1 (mTORC1). These transcription factors control the expression of genes involved in cell survival, proliferation, and metabolism.

Translation regulation is another important aspect of the Akt pathway. Akt activates the protein synthesis machinery by phosphorylating and inhibiting the activity of glycogen synthase kinase-3β (GSK3β). This leads to the activation of the translation initiation factor eIF-4E and subsequently enhances the translation of specific mRNAs involved in cell growth and survival.

Ubiquitin-related molecules play a role in regulating the Akt pathway through protein degradation. Activation of the Akt pathway inhibits glycogen synthase kinase-3β (GSK3β), leading to the stabilization and accumulation of β-catenin. β-catenin then enters the nucleus and forms a complex with the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors. This complex regulates the expression of genes involved in cell proliferation and survival.

Research Tools for Akt Pathway

At Creative BioMart, we understand the importance of having high-quality research tools to study the Akt pathway and its associated molecules, so we offer a variety of recombinant proteins, cell and tissue lysates, protein pre-coupled beads, and other products to help researchers better understand the Akt pathway and its role in various cellular processes.

In addition to our catalog products, Creative BioMart also offers custom services to meet specific research needs. Our team of experienced scientists can provide tailored solutions, including protein expression, purification, and characterization, as well as assay development and cell-based functional studies. With our custom services, researchers can obtain unique reagents and experimental tools to further investigate the Akt pathway and its role in specific cellular processes. Please click on the relevant aspect molecule/target to view all research reagents.

Adaptor Proteins in the Akt Pathway
Intracellular Kinases in the Akt Pathway
Phosphatases in the Akt Pathway
Phospholipases, Small GTPases, and Other Molecules in the Akt Pathway
Receptor Tyrosine Kinases (RTKs) in the Akt Pathway
Transcription Factors in the Akt Pathway
Translation Regulation by the Akt Pathway
Ubiquitin-related Molecules in the Akt Pathway

In addition to providing research tools, Creative BioMart also offers a wide range of technical and educational resources to assist researchers in better understanding and applying these tools. We integrate these tools and resources for easy access and retrieval of relevant information, including literature, technical guides, and operation protocols, enabling researchers to better utilize these research tools for scientific inquiry.

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