Contents

1 Introduction   **FREE**
	Introduction  Overview of cell signalling mechanisms  Communication through electrical signals  Communication through chemical signals ON mechanisms Cell stimuli Receptors Transducers and amplifiers Intracellular messengers Sensors and effectors OFF mechanisms  Information transfer mechanisms Conformational-coupling mechanisms Post-translational modifications Protein methylation Protein degradation DNA methylation Desensitization of cell signalling Spatial and temporal aspects of cell signalling Signalsome  References
2 Cell signalling pathways
	Synopsis  Intracellular signalling pathways  Cyclic AMP signalling pathway Cyclic AMP formation Adenylyl cyclase (AC) Cyclic AMP signalling effectors Protein kinase A (PKA) Exchange proteins activated by cyclic AMP (EPACs) Cyclic AMP signalling functions Cyclic AMP hydrolysis Cyclic AMP efflux  GTP-binding proteins Heterotrimeric G proteins Monomeric G proteins  Ca2+ signalling Basic mechanism of Ca2+ signalling Ca2+ signalling signalsome Ca2+ signalling modules Ca2+ ON reactions Ca2+-induced Ca2+ release (CICR) Ca2+ OFF reactions Ca2+ buffers Ca2+ signalling function Spatiotemporal aspects of Ca2+ signalling  Cyclic ADP-ribose (cADPR) signalling cADPR working hypothesis cADPR generation and metabolism cADPR control of Ca2+ release cADPR and cell regulation  Nicotinic acid–adenine dinucleotide phosphate (NAADP) signalling NAADP generation and metabolism NAADP control of Ca2+ release  Phosphoinositide signalling Phosphoinositide metabolism Inositol lipid metabolism Inositol phosphate metabolism Inositol 1,4,5-trisphosphate (InsP3)/Ca2+ signalling cassette Phospholipase C (PLC) Diacylglycerol (DAG)/protein kinase C (PKC) signalling cassette Protein kinase C (PKC) Phosphoinositide lipid signalling molecules PtdIns4,5P2 signalling cassette PtdIns 3-kinase signalling Insulin receptor Multipurpose inositol polyphosphate signalling pathway Nitric oxide (NO)/cyclic GMP signalling pathway Cyclic GMP signalling pathway Reactive nitrogen species (RNS) signalling Redox signalling Reactive oxygen species (ROS) signalling  Mitogen-activated protein kinase (MAPK) signalling Overview Mitogen-activated protein kinase (MAPK) signalling toolkit Extracellular-signal-regulated kinase (ERK) pathway c-Jun N-terminal kinase (JNK) pathway p38 pathway Mitogen-activated protein kinase (MAPK) signalling properties  Nuclear factor kB (NF-kB) signalling pathway Nuclear factor kB (NF-kB) signalling toolkit Tumour necrosis factor a (TNFa) signalling pathway Toll receptor signalling pathway  Phospholipase D (PLD) signalling pathway Phospholipase D (PLD) activation Phosphatidic acid (PA) action Phosphatidic acid (PA) metabolism  Sphingomyelin signalling pathway Generation of ceramide and sphingosine 1-phosphate (S1P) Sphingosine 1-phosphate (S1P) Ceramide  Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway Janus kinase (JAK)/signal transducer and activator of transcription (STAT) structure Signal transducer and activator of transcription (STAT) activation cascade Suppressor of cytokine signalling proteins (SOCS) Janus kinase (JAK)/signal transducer and activator of transcription (STAT) function in growth and development  Smad signalling pathway Smad signalling toolkit Domain structure of the Smad family Smad signalling mechanism Transforming growth factor b (TGF-b) receptor activation Smad activation of transcription Modulation of Smad signalling Transforming growth factor b (TGF-b) inhibition of cell proliferation  Wnt signalling pathways Wnts Canonical Wnt/b-catenin pathway Wnt/planar cell polarity (PCP) pathway Wnt/Ca2+ signalling pathway Casein kinase I (CKI)  Hedgehog signalling pathway Hedgehog signalling toolkit Hedgehog activation of transcription Hedgehog signalling functions  Notch signalling pathway Modulation of Notch signalling  Endoplasmic reticulum (ER) stress signalling Unfolded protein response (UPR) Endoplasmic reticulum (ER) overload response (EOR) Activation of apoptosis  Metabolic messengers  AMP signalling pathway Adenosine monophosphate (AMP) AMP-activated protein kinase (AMPK) Adenosine triphosphate (ATP) Bicarbonate (HCO3-) Fatty acids NAD signalling pathways Sterol sensing and cholesterol biosynthesis  References
3 Ion channels
	Synopsis  Ca2+ entry channels Voltage-operated channels (VOCs)  Voltage-operated channel (VOC) terminology and classification Voltage-operated channel (VOC) structure Voltage-operated channel (VOC)-associated subunits Voltage-operated channel (VOC) properties Voltage-operated channel (VOC) distribution and function  CaV1 family of L-type channels CaV1.1 L-type channel Modulation of the CaV1.1 L-type channel CaV1.2 L-type channel CaV2 family of N-type, P/Q-type and R-type channels CaV3 family of T-type channels  Agonist-operated channels (AOCs) Receptor-operated channels (ROCs) Cysteine-loop receptors Structure and function of nicotinic acetylcholine receptors (nAChRs) Glutamate receptors Second messenger-operated channels (SMOCs) Arachidonic acid-regulated Ca2+ (ARC) channel Store-operated channels (SOCs)  Transient receptor potential (TRP) ion channel family Structural organization of the transient receptor potential (TRP) ion channel family Canonical transient receptor potential (TRPC) family Vanilloid transient receptor potential (TRPV) family Melastatin-related transient receptor potential (TRPM) family Mucolipin transient receptor potential (TRPML) family TRPA1 Temperature sensing Polycystins  Mechanosensitive channels  K+ channels Ca2+-sensitive K+ channels K+ channel structure Large-conductance (BK) channel opening Intermediate-conductance (IK) and small-conductance (SK) channel opening G protein-activated inwardly rectifying K+ (GIRK) channels ATP-sensitive K+ (KATP) channels Hyperpolarizing-activated cyclic nucleotide-gated (HCN) channels  Chloride channels and transporters Ca2+-sensitive Cl- channels (CLCAs) CLC chloride channels and transporters  ATP-binding cassette (ABC) transporters ABCA1 ABCA2 ABCA3 ABCA4 ABCB4 ABCC1 ABCC4 ABCC7 ABCD1 Cystic fibrosis transmembrane conductance regulator (CFTR)  Cation-chloride cotransporters Na+-K+-2Cl- cotransporter 1 (NKCC1) Na+-K+-2Cl- cotransporter 2 (NKCC2) Na+-Cl- cotransporter (NCC) K+-Cl- cotransporter 1 (KCC1) K+-Cl- cotransporter 2 (KCC2) K+-Cl- cotransporter 3 (KCC3) K+-Cl- cotransporter 4 (KCC4)  WNK protein kinase WNK1 WNK2 WNK3 WNK4  Cell volume regulation  Aquaporins  Ca2+ release channels Ryanodine receptors (RYRs) Inositol 1,4,5-trisphosphate receptors (InsP3Rs) Luminal regulation of Ca2+ release channels  References
4 Sensors and effectors
	Synopsis  Sensors  Ca2+ sensors Calmodulin (CaM) Troponin C (TnC) Neuronal Ca2+ sensor (NCS) proteins Ca2+-binding proteins (CaBPs) Annexins S100 proteins Synaptotagmins  Effectors Ca2+ effectors Phosphorylase kinase Myosin light chain kinase (MLCK) Calcineurin (CaN)  Exocytosis Exocytotic mechanisms Exocytotic/endocytotic cycle Kiss-and-run vesicle fusion Exocytosis triggered by Ca2+ entry through voltage-operated channels (VOCs) Exocytosis triggered by Ca2+ release from internal stores Exocytotic machinery Ca2+-dependent exocytosis  Phagocytosis Phagosome maturation  Gene transcription Transcription factor classification Transcription factor activation mechanisms Gene silencing Developmentally regulated transcription factors Nuclear receptors Internal signal-dependent transcription factors  Cell-surface receptor-dependent transcription factors Activation of transcription by cytosolic signals b-Catenin Signal transducers and activators of transcription (STATs) Nuclear factor of activated T cells (NFAT) Nuclear factor kB (NF-kB) Single-minded 1(Sim1) Smads Activation of transcription by nuclear signals Activation of transcription factors by regulating their expression  Signalsome stability  Ciliary beating Primary cilium  Actin remodelling Wiskott–Aldrich syndrome protein (WASP) Wiskott–Aldrich syndrome protein (WASP) verprolin homologous (WAVE) Actin-related protein 2/3 complex (Arp2/3 complex) Ena/vasodilator-stimulated phosphoprotein (VASP) family  References
5 Off mechanisms
	Synopsis  Protein phosphatases Protein tyrosine phosphatases (PTPs) Protein serine/threonine phosphatases  Phosphodiesterase (PDE) PDE1 PDE2 PDE3 PDE4 PDE5 PDE6  Ca2+ pumps and exchangers Pump classification Properties of Ca2+ pumps Organization and distribution of Ca2+ pumps  Mitochondria Generation of ATP Mitochondrial Ca2+ uptake Mitochondrial Ca2+ release Endoplasmic reticulum (ER)/mitochondrial Ca2+ shuttle Mitochondrial permeability transition pore (MTP) Mitochondrial modulation of Ca2+ signals Ca2+ modulation of mitochondrial function Mitochondrial motility  References
6 Spatial and temporal aspects of signalling
	Synopsis  Spatial organization of signalling pathways Signal transduction domains Scaffolding/targeting proteins Macromolecular signalling complexes  Lipid rafts and caveolae Lipid composition of rafts and caveolae Caveolae structure Signalling function of caveolae  Cadherins Classical cadherins Catenins Desmosomal cadherins Protocadherins Atypical cadherins  Cell adhesion complexes Focal adhesion complex Focal adhesion actin attachment Focal adhesion integrin signalling Podosome  Local and global aspects of signalling Elementary and global aspects of Ca2+ signalling Cyclic AMP microdomains Reactive oxygen species (ROS) microdomains  Temporal aspects of signalling Cellular oscillators Brain rhythm Membrane oscillators Cytosolic oscillators  References
7 Cellular processes
	Synopsis  Mammalian cell types  Metabolic energy network Control of food intake and body weight  Glial cells  Astrocytes Astrocyte structure Neuronal–astrocyte communication Astrocyte–neuronal communication Astrocyte excitability Astrocyte regulation of cerebral blood flow  Microglia Neuronal–microglia interactions  Endothelial cells Endothelial regulation of paracellular permeability  Skeletal muscle Skeletal muscle structure Excitation–contraction (E-C) coupling in skeletal muscle Excitation–metabolism coupling in skeletal muscle Insulin control of skeletal muscle glycogen synthesis  Cardiac cells Sinoatrial node pacemaker cells Ventricular cells Atrial cells  Smooth muscle cells Smooth muscle cell structure Smooth muscle cell excitation–contraction coupling Smooth muscle Ca2+ signalling Smooth muscle Rho/Rho kinase signalling Smooth muscle cell relaxation Nitric oxide (NO)/cyclic GMP and smooth muscle relaxation Smooth muscle cell Ca2+ sparks Smooth muscle activation mechanisms Vas deferens Uterine smooth muscle cells Detrusor smooth muscle cell Ureter smooth muscle cell Airway smooth muscle cells Vascular smooth muscle cells Smooth muscle cell cytosolic oscillator Corpus cavernosum smooth muscle cells Gastrointestinal smooth muscle cells Urethral smooth muscle cells Interstitial cells of Cajal Phase wave  Ca2+ homoeostasis Hormonal regulation of Ca2+ homoeostasis Ca2+ reabsorption by the intestine  Bone Bone remodelling