Cell Signaling & Neuroscience Signaling by Inositol Phospholipids

Slides Programmed Cell Death Activation and Inhibition of Apoptosis Mitochondria in Apoptosis ATM/p53 Signaling Pathway Caspase Cascade Caspase Activation Intrinsic Pathway Granzyme B FAS and Related Proteins Fas Signaling G1, and S Phases G2 and M Phases Regulatory Cascade The p53 Signaling Pathway Cytokines and Growth Factors Structures of Activin and Inhibin Structures of Chemokine Receptors Angiopoietins EGFR Signaling Pathway Transmembrane Precursors of EGF Possible Receptor Combos and Ligand Actions of Flt-3/Flk-2 Hedgehog and BMI1 IGF Regulation of Apoptosis IL-13 and IL-4 receptor IL-18 Production Neurotrophins and Their Receptors TrkA GDNF Family with Receptors PDGF Receptors and Actions TGF-beta Signaling BMP Signaling TNF Signaling TNF-α and TNF-β Proposed Balance Between TNF Superfamily Structure of Receptors VEGF Receptor and Ligands Prolactin Regulation Insulin Pathway Glucocorticoid Receptor Signaling Vascular Endothelial Cell Interactions Integrin Signaling in Cell Survival VEGF Receptor Signaling MMPs and Cytokines Events Leading to Angiogenesis Transcription Factors Nuclear Complex Targeting Jak/Stat Pathway STAT3 PPAR Formation of Nucleosomes DNA Compaction Early Response Events Cell Cycle Checkpoint Linkage between DNA Repair and Chromatin Modification Functions of WRN, BLM and MRE11 mRNP Transport Importinα - Importinβ Pathway Modular Structure of Transcription factors Transcription Activation by Nuclear Receptors Coupled RNA Splicing and Nuclear Export RNA Polyadenylation Mammalian mRNA Polyadenylation RNA Maturation Epigenetic Control Phosphorylation-driven Initiation-Elongation cAMP Metabolism cGMP Metabolism G-Protein Signaling T Cell Receptor B Cell Receptor Monovalent Ion Channels Activation/Inactivation Ligand-Gated Ion Channel Aquaporin Channel Structure Calcium Channel Structure Calcium Channel Pore Region Chloride Channel HCN Channel 2TM Potassium Channel Structure 6TM Potassium Channel Structure Sodium Channel Structure Sodium Channel Pore Region PTEN Pathway Lipids in Cell Signaling Inositol Phosphates Phosphatidic Acid Inositol Phospholipids ABC Transporters ABC-ATPases BSEP MRP1 β-Amyloid Plaques Notch Secretase Second Messenger Systems Limbic Reward Circuit Major Pathways in the CNS Endothelin Signaling NPY and Catecholamines Ascending Pain Pathway Modulation of Pain Transmission Mechanism of Action Fig. A Mechanism of Action Fig. B Drug Activation of Dopaminergic GABAB Receptor Oxidative Stress nNOS eNOS iNOS Nitric Oxide Proteasome/Ubiquitination Formation of Activated 20S Proteasome Ubiquitin Pathway MAP Kinase Cascades AKT Signaling Pathways Activated by VEGF

Signaling by Inositol Phospholipids

When bound by nerve growth factor (NGF), the high affinity NGF receptor, TrkA, autophosphorylates tyrosine residues in its cytoplasmic domain. The activated receptor binds to and activates phospholipase Cg (PLCg), which cleaves membrane-bound phosphatidylinositol-bisphosphate (PIP₂) to generate D-myo-inositol-1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG). IP₃ diffuses from the plasma membrane to its receptor on the surface of the endoplasmic reticulum (ER) that is coupled to a Ca²⁺-release channel in the ER membrane. There it stimulates the release of Ca²⁺ from ER stores resulting in an increase in the cytosolic concentration of Ca²⁺. Cytosolic Ca²⁺ is then available for binding to calmodulin or to various Ca²⁺-binding cytoskeletal proteins involved in microtubule and intermediate filament formation. Many of the enzymatic effects of the released Ca²⁺ are mediated through protein phosphorylations catalyzed by a family of Ca²⁺/calmodulin dependent protein kinases (CaMK-II/IV).

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References:

Carpenter, G., and Ji, Q.S., Phospholipase Cg as a signal-transducing element. Exp. Cell Res., 253, 15-24 (1999).

Patel, S., et al., Molecular properties of inositol 1,4,5-trisphosphate receptors. Cell Calcium, 25, 247-264 (1999).

Takei, K., et al., Regulation of nerve growth mediated by inositol 1,4,5-trisphosphate receptors in growth cones. Science, 282, 1705-1708 (1998).