Cell Signaling & Neuroscience T Cell Receptor (TCR)

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

T Cell Receptor (TCR) Signaling

One of the first steps in the generation of the immune response is the recognition by T lymphocytes of peptide fragments (antigens) derived from foreign pathogens that are presented on the surface of antigen presenting cells (APC). This event is mediated by the T cell receptor (TCR), which transduces these extracellular signals by initiating a wide array of intracellular signaling pathways. One of the first biochemical events following TCR activation is the activation of Src family tyrosine kinases (p56^lck) that, in turn, phosphorylate phospholipase Cg₁ (PLCg₁). Activation of PLCg₁ leads to hydrolysis of phosphatidylinositol 4, 5-bisphosphate (PIP₂), generating diacylglycerol (DAG) and inositol trisphosphate (IP₃). DAG activates protein kinase C (PKC) that, in turn, phosphorylates Ras, a GTPase that activates Raf leading to recruitment of the MAP kinase cascade. IP₃ releases calcium from its intracellular stores in the endoplasmic reticulum (ER). The Ca²⁺ binds to calmodulin that, in turn, activates calcineurin, a Ca²⁺/calmodulin dependent protein phosphatase. NFAT, a transcriptional regulator of interleukin-2 (IL-2) gene expression, is a direct target of calcineurin. Calcineurin dephosphorylates the cytosolic component of NFAT, NFATc, which migrates to the nucleus and induces transcription of the IL-2 gene.

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References:

Samelson, L.E., et al., Signal transduction mediated by the T-cell antigen receptor. Ann. NY Acad. Sci., 7, 157-172 (1995).

Hama, N., et al., Calcium/calmodulin-dependent protein kinase II down regulates both calcineurin and protein kinase C-mediated pathways for cytokine gene transcription in human T cells. J. Exp. Med., 181, 1217-1222 (1995).

Germain, R.N., and Stefanova, I., The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. Annu. Rev. Immunol., 17, 467-522 (1999).