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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
+
O
CH3-N-CH2CH2O-C-CH3
CH3
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
Tyrosinespecific
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)
AC
Forskolin
Gsa
GTP
Self-inactivation of Gs
AC
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
Color
Blindness
red- or greendichromats
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
CDK2
Cyclin
Glu51
(mask active site)
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