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 Glycobiology10 Nucleotides and Nucleic Acids11 Lipids12 Biological Membranes and Transport13 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 ChannelsIon 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
CH3 O+
Voltage-Gated Ion Channels Produce Neuronal Action Potential
Neurons Have Receptor Channels That Respond to A Variety of Neurotransmitters
Glycine, glutamate, serotonin,-aminobutyric acid (GABA)
Receptor Enzymes
Tyrosine-specific proteinkinase
Regulation of gene expression by insulin
Activation of glycogen synthase by insulin
Guanylyl Cyclase is a Receptor Enzyme that Generates The Second Messenger cGMP
Atrial Natriuretic Factor Heart ANF Kidney ANF/ANFR cGMP
Na+/H2O out
(diarrhea)
cGMP-dependent protein kinase PKG
G protein-Coupled Receptors and Second Messengers
Serpentine receptors
-adrenergic receptor
Gs:Stimulatory G protein(, and subunits)
(Adrenaline)
Interaction of Gs with adenylyl cyclase (AC)
AC
Gs
GTP
Forskolin
Self-inactivation of Gs
AC
Activation of cAMP-dependent protein kinase, PKA
a C subunit of PKA
PKI
ATP
Epinephrine Cascade
Degradation of cAMP by Cyclic Nucleotide Phosphodiesterase
Desensitization of the -Adrenergic Receptor
-arrestin
Two Second Messengers Are Derived from Phosphatidylinositols
(IP3)
Diacylglycerol (DG)
Protein kinase C (PKC)
Gq
Phospholipase C
Calcium Is a Second Messenger in Many Signal Transductions
Cytosolic [Ca2+] < 10-7 M
norepinephrine
A single hepatocyteThymocytes (loaded with fura dye)
Calmodulin (CaM)
CaM kinase II peptide
Sensory Transduction in Vision, Olfaction, and Gustation
Light reception in the vertebrate eye
(colors)
(low levels of light)
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( subunits)
Molecular consequences of photon absorption by rhodopsin
Cone cells specialize in color vision – different opsins
Color 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 estrogen- breast cancer treatment
Antagonist of progesterone- terminate early pregnancies
Antagonist of steroid hormones as drugs
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)
ATP
CDK2
Cyclin
P-Thr
Glu51
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
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