1、Cell Signal Transduction,Junling Liu,School of Medicine Shanghai Jiao Tong University2015.4.29,What is cell signal transduction?,Small cell lung carcinoma,Osteoporosis,CAD,Cell communication and signal transduction-Molecular Pathophysiology,Insulin functions,Basic Profiles of Cell Signal Transductio
2、n,The response of a particular cell to a signal depends on the type of proteins it contains.,Signal,Receptor,Signal transduction pathway,Gene expression,Profile of a signaling component,Signaling molecules operate over various distances in animals,Seven major classes of membrane receptors,Cytoskelet
3、al Rearrangement,Changes in gene expression,Cell Cycle Arrest,Effector Protein,Cell Response to the Signal: Effector Proteins,Protein-Protein Interaction,Protein phosphorylation,Protein Ubiquitination,Protein sumoylation,Protein acetylation,Protein post-translation modification,Dynamic and Reverse,C
4、lassical cell signaling pathway,Example 1: Integrin IIb3 Mediates Dual-directions Signaling Transduction and Platelet Activation,Aggregation,Spreading,Clots Retraction,Integrin IIb3-Mediated Signaling and Hemostasis,Anti-platelet drugs,Nigel Mackman, Nature 2008;451,21 ,914-918,Percutaneous Coronary
5、 Intervention (PCI),Therapy of Acute Coronary Syndromes (ACS),Example 2: Biology of PI3K/Akt signaling pathway,Gerrit van Meer, Dennis R. Voelker & Gerald W. Feigenson. Membrane lipids: where they are and how they behave. Nature Reviews Molecular Cell Biology 9, 112-24,mammals yeast,Signaling lipids
6、 1% total phospholipidPIP2 in plasma membrane,PIPIPPIP2,5%,.5%,.05%,109 phospholipids in plasma membrane,Lipid composition varies among cell membranes,Lipid hydrolysis,Nature Reviews Drug Discovery 8, 627-644 (August 2009). Liu P et al,Important role of PI3K/Akt signaling pathway,Nature Reviews Drug
7、 Discovery 8, 627-644 (August 2009). Liu P et al,PI3K family,Newton, A. C. J. Lipid Res. 2009;50:S266-S271,Protein kinase B/Akt,Receptors mediated Akt activation and its functions,Basic regulators of PI3K/Akt signaling pathway,PTEN, MMAC1, mutated in multiple advanced cancers 1,PI3-kinase is opposed
8、 by lipid phosphatase PTEN,mTOR functions in two distinct complexes and pathways,PI3K Signaling Inhibitors Tested,PI3K Signaling Inhibitors Tested for Cancer Chemotherapy,Insulin mediated PI3K Signaling and Diabetes,Platelets GPVI mediated PI3K/Akt Signaling and Arthritis,Platelet adhesive receptor
9、GPVI mediated signaling,PROTEOMICS, Annual Review of Genomics and Human Genetics, Vol. 5: 267-293, 2004,Large Scale Investigation of Cell Signaling,GENOMICS,Metabonomic Network,CellDesigner is a structured diagram editor for drawing gene-regulatory and biochemical networks. Intuitive user-interface
10、helps you to draw a diagram in rich graphical representation with your own design.,CellDesigner: Version 4.1 http:/celldesigner.org/features.html free download,SNAVI: Desktop Application for Analysis and Visualization of Large-Scale Cell Signaling Networks,Softwares,Useful website,Professor Sir Mich
11、ael Berridge, FRS,http:/www.biochemj.org/csb/default.htm,“A fantastic resource for educators and researchers alike, and for anyone interested in the basics and details of cell signalling pathways. The diagrams are particularly useful as teaching tools, I highly recommend this to anyone engaged in si
12、gnalling research“. Alex Toker, Harvard Medical School, Boston,Contents 1 Introduction 2 Cell signalling pathways 3 Ion channels 4 Sensors and effectors 5 Off mechanisms 6 Spatial and temporal aspects of signalling 7 Cellular processes 8 Development 9 Cell cycle and proliferation 10 Neuronal signall
13、ing 11 Cell stress, inflammatory responses and cell death 12 Signalling defects and disease,Cell Signalling Biology,How to study?,MAPK signaling,Smad signaling,Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2009,Wnt signaling pathways,Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2009,Stimuli for enzyme-linked receptors,NCBI（http:/www.ncbi.nlm.nih.gov/）Signaling Transduction：,Go to：http:/www.ncbi.nlm.nih.gov/ncicgap/,KEGG: Kyoto Encyclopedia of Genes and Genomes - GenomeNet,http:/ pathway DIY,Any questions?,
