Download BIO 330 Cell Biology Lecture Outline Spring 2011 Chapter 14

BIO 330 Cell Biology
Lecture Outline
Spring 2011
Chapter 14: Signal Transduction – Messengers and Receptors
I. Overview of Chemical Signals and Receptors
A. Types of chemical signals
Endocrine
Paracrine
Juxtacrine
Autocrine
B. Receptors
Ligands
Second messengers
Signal transduction
Membrane vs. intracellular receptors
Peptide vs. hydrophobic ligands
C. Binding between receptors and ligands
Ligands bind their cognate receptors at the binding site
Receptor is “occupied” when ligand is bound
Amount of receptor binding is proportional to concentration of free ligand
Similar to enzyme kinetics
Receptor affinity
Dissociation constant, Kd , is the concentration of free ligand required to occupy
half the receptors present (similar to Km for enzymes)
Receptor down-regulation
Receptor-mediated endocytosis
Desensitization
Agonists vs. antagonists
Can be used as drugs to treat medical problems
D. Signal transduction cascades
Signaling integration
Converging vs. diverging signaling cascades
Signal amplification
II. G-protein Coupled Receptors (GPCRs)
A. Structure of GPCRs
7 membrane-spanning segments
Intracellular segment interacts with G proteins (guanine-nucleotide binding protein)
B. Activation and inactivation of G proteins
 subunits dissociate and cause a variety of signaling cascades
Types of  subunits
C. Second messengers
1. Cyclic AMP (cAMP) pathway
2. Inositol triphosphate and diacylglycerol pathway
BIO 330 Cell Biology
Lecture Outline
Spring 2011
IP3 leads to increased intracellular Ca2+
DAG leads to PKC activation
3. Nitric oxide
D. Transduction of signals via  subunits of G proteins
III. Protein Kinase-Associated Receptors
A. Tyrosine vs. serine/threonine kinases
B. Growth factors bind protein-kinase associated receptors
C. Receptor tyrosine kinases (RTKs)
Structure
Activation
Signal transuduction cascade
Ras and MAP kinase
Other pathways
Role of scaffolding complexes
Dominant negative mutants in research
D. Receptor Ser/Thr kinases
TGF-b family (transforming growth factor)
Smads are used in intracellular signaling
DNA binding proteins
E. CREB and STATs (Chapter 23; pp. 742-742)
Examples of transcription factors activated by intracellular signal transduction
IV. Intracellular Receptors (Chapter 23; pp. 739-741)
A. Steroid hormone receptors
Transcription factors
Hormone response elements
DNA binding domains
V. Hormonal Signaling
A. Hormone definition
Endocrine product released into the bloodstream to act on a distant target tissue
B. Control of glucose metabolism as an example
Adrenergic receptors
Insulin pathway
VI. Cell Signaling and Apoptosis
A. Programmed cell death sequence of events
DNA segregates, cytoplasm shrinks
Membrane blebs, nucleus & organelles fragment
Cell is dismantled into apoptotic bodies
BIO 330 Cell Biology
Lecture Outline
Spring 2011
Cellular debris is engulfed by macrophages
B. Caspases
Master regulators of apoptosis (cysteine and aspartic acid residues are vital to activity)
Procaspases are activated by cleavage
Caspases then cleave other proteins
C. Signaling pathways leading to apoptosis
Cell death signals
TNF and CD95/Fas
Initiator caspases vs. executioner caspases
Mitochondria
Bcl-2: anti-apoptotic vs. pro-apoptotic proteins
Cytochrome c
p53