Part II Structure and Catalysis 5 Amino Acids, Peptides, and Proteins 6 The Three-Dimensional Structure of Proteins 7 Protein Function 8 Enzymes 9 Carbohydrates and Glycobiology 10 Nucleotides and Nucleic Acids 11 Lipids 12 Biological Membranes and Transport 13 Biosignaling

Chapter 13 Biosignaling

Molecular Mechanisms of Signal Transduction

Scatchard Plot: Quantifies the Receptor-Ligand Interaction R + L RL

Four general types of signal transducers

Gated Ion Channels Ion Channels Underlie Electrical Signaling in Excitable Cells Transmembrane electrical potential

The Nicotinic Acetylcholine Receptor is a Ligand-Gated Ion Channels CH3-N-CH2CH2O-C-CH3 CH3 O +

Voltage-Gated Ion Channels Produce Neuronal Action Potential Neurons Have Receptor Channels That Respond to A Variety of Neurotransmitters Glycine, glutamate, serotonin, g-aminobutyric acid (GABA)

Receptor Enzymes Tyrosine- specific protein kinase

Regulation of gene expression by insulin

Activation of glycogen synthase by insulin

Guanylyl Cyclase is a Receptor Enzyme that Generates The Second Messenger cGMP (diarrhea) cGMP-dependent protein kinase PKG Atrial Natriuretic Factor Heart ANF Kidney ANF/ANFR cGMP Na+/H2O out

G protein-Coupled Receptors and Second Messengers (Adrenaline) Serpentine receptors b-adrenergic receptor Gs: Stimulatory G protein (a, b and g subunits)

Interaction of Gsa with adenylyl cyclase (AC) Forskolin GTP

Self-inactivation of Gs

Activation of cAMP-dependent protein kinase, PKA ATP PKI a C subunit of PKA

Epinephrine Cascade

Degradation of cAMP by Cyclic Nucleotide Phosphodiesterase

Desensitization of the b-Adrenergic Receptor b-arrestin

Two Second Messengers Are Derived from Phosphatidylinositols Gq Phospholipase C (IP3) Diacylglycerol (DG) Protein kinase C (PKC)

Calcium Is a Second Messenger in Many Signal Transductions Thymocytes (loaded with fura dye) A single hepatocyte norepinephrine Cytosolic [Ca2+] < 10-7 M

Calmodulin (CaM) CaM kinase II peptide

Sensory Transduction in Vision, Olfaction, and Gustation Light reception in the vertebrate eye (low levels of light) (colors) inner outer segment (visual cortex of the brain)

Light-induced hyperpolarization of rod cells (Light induces degradation of cGMP)

Likely structure of rhodopsin complexed with G protein transducin 11-cis-retinal opsin (rhodopsin) transducin (abc subunits)

Molecular consequences of photon absorption by rhodopsin

Cone cells specialize in color vision – different opsins Blindness red- or green- dichromats

Vertebrate Olfaction, and Gustation Use Mechanisms Similar to the Visual System

Common features of signaling systems that detects hormones, light, smells, and tetastes

Toxins produced by bacteria that cause cholera and whooping cough (pertussis)

Regulation of Transcription by Steroid Hormons

Antagonist of steroid hormones as drugs Antagonist of estrogen - breast cancer treatment Antagonist of progesterone - terminate early pregnancies

Regulation of Cell Cycle by Protein Kinases Eukaryotic cell cycle

Activation of cyclin-dependent protein kinase (CDKs) by cyclin and phosphorylation T loop (mask active site) Glu51 CDK2 P-Thr ATP

Variation in the activities of specific CDKs during the cell cycle in animals

Regulation of CDK by phosphorylation and proteolysis DBRP: destruction box recognizing protein

Regulation of cell division by growth factors

Regulation of passage from G1 to S by phosphorylation of pRb pRb, retinoblastoma protein

Oncogenes, Tumor Suppressor Genes, and Programmed Cell Death Oncogenes are mutant forms of the genes for protein that regulate the cell cycle Conversion of a regulatory gene into a viral oncogene

Oncogene-encoded defective EGF receptor Breast, stomach, and ovary cancers

From Normal Epithelial Cell to Colorectal Cancer

Initial events of apoptosis