Lecture 03 General aspects of molecular signaling pathways

Lecture 03  General aspects of molecular signaling pathways

Lecture 03 General aspects of molecular signaling pathways and cellular signaling BIOL 5190/6190 Cellular & Molecular Singal Transduction Prepared by Bob Locy Last modified -13F G Protein Coupled Receptor Pathways 1. G Protein Coupled Receptors

Seven membrane-spanning domain receptors Heterotrimeric G-proteins Activate different second-messenger systems cyclic AMP based IP3 based Second messengers work to modulate effectors that mediate cellular responses

General principle of the GPCR signaling system. Vilardaga J et al. J Cell Sci 2010;123:4215-4220 2010 by The Company of Biologists Ltd GPCRs Vilardaga J et al. J Cell Sci 2010;123:4215-4220

Modulation of G-protein signaling by receptor heterodimers. Vilardaga J et al. J Cell Sci 2010;123:4215-4220 2010 by The Company of Biologists Ltd Module 1: Figure stimuli for cyclic AMP signalling Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

Module 1: Figure stimuli for InsP3/DAG signalling Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Tyrosine and histidine kinases Histidine kinase receptors are among most widely known types of receptors. Also known as phosphorelay receptors

Figure 1 Two-component histidine kinases and more complex phosphorelay systems Biochemical Society Transactions (2013) 41, 1023-1028 - Paul V. Attwood www.biochemsoctrans.org Approximately 20 different Receptor Tyrosine Kinase classes have been identified. [KEGG, 2010] RTK class I (EGF receptor family) (ErbB

family) RTK class X (LTK receptor family) RTK class II (Insulin receptor family) RTK class XI (TIE receptor family) RTK class III (PDGF receptor family) RTK class XII (ROR receptor family) RTK class IV (FGF receptor family) RTK class XIII (DDR receptor family)

RTK class V (VEGF receptors family) RTK class XIV (RET receptor family) RTK class VI (HGF receptor family) RTK class XV (KLG receptor family) RTK class VII (Trk receptor family) RTK class XVI (RYK receptor family) RTK class VIII (Eph receptor family)

RTK class XVII (MuSK receptor family) RTK class IX (AXL receptor family) Tyrosine and Histidine Kinase Receptors The intracellular C-terminal region displays the highest level of conservation and comprises catalytic domains responsible for the kinase activity of these receptors,

which catalyses receptor autophosphorylation and tyrosine phosphorylation of RTK substrates. The extracellular N-terminal region exhibits a variety of conserved elements including immunoglobulin (Ig)-like or epidermal growth factor (EGF)-like domains, fibronectin type III repeats, or cysteine-rich regions that are characteristic for each subfamily of RTKs; these domains contain primarily a ligand-binding site, which binds

extracellular ligands, e.g., a particular growth factor or hormone. Each monomer has a single hydrophobic transmembranespanning domain composed of 25-38 amino acids, an extracellular N-terminal region, and an intracellular Cterminal region. Most RTKs are single subunit receptors but some exist as multimeric complexes, e.g., the insulin receptor that forms disulfide-linked dimers in the absence of hormone

Ligand binding to the extracellular domain often induces formation of receptor dimers. Tyrosine and Histidine Kinase Receptors Module 1: Figure stimuli for enzyme-linked receptors Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

Module 1: Figure tyrosine kinase-linked receptors Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012 Module 1: Figure PDGFR activation Cell Signalling Biology - Michael J. Berridge - www.cellsignallingbiology.org - 2012

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