Midterm 3 Flashcards
What are the general principles of extracellular signal to cellular response?
- Synthesis of signaling molecule
- Release of the signaling molecule via exocytosis
- Transit of signaling molecule to the target cell
- Binding of signaling (ligand) to a protein receptor on the target cell
- Binding of ligand to receptor results in a conformational change of the receptor
- Receptor initiates one or more intracellular pathway (cellular function, metabolism, gene expression, shape, movement)
- Deactivation of receptor
- Removal of ligand
What are the 4 types of intercellular signaling?
- endocrine
- paracrine
- autocrine
- juxtacrine
What are the three main classes of cell surface receptors?
- G-protein coupled (GPCR)
- Enzyme-linked
- Ion Channel-linked
What are the two basic types of cell signaling? (Receptors)
- cell surface receptors
- intracellular receptors
What are the properties of intracellular receptors?
-small hydrophobic signaling molecules can diffuse across the plasma membrane and bind to receptor proteins either in the cytoplasm or nucleus
What are the two types of intracellular receptors?
- cytoplasm
- nucleus
What are second messengers?
-small substances that activate (or inactivate) specific proteins
What are two types of signaling pathways shown after the binding of a ligand to a receptor?
- receptor binds to an effector and generates a soluble and diffusable intracellular second messenger
- recruit proteins to their intracellular domains at the plasma membrane
What is a GAP?
GTPase-activating protein
What is a GEF?
Guanine nucleotide exchange factor
What are the 3 subunits of a G protein?
- alpha
- beta
- gamma
What does the G protein act as when it couples with the receptor? (What part couples?
- alpha subunit
- acts as a GEF
Where is the amino terminus of the G protein-coupled receptor located?
On the outside of the cell
What does GRK stand for?
G protein coupled receptor kinase
What is the general structure of a G protein-coupled receptor?
- 7 transmembrane alpha helixes
- ligand binding site
- cytosol is portion that interacts with G proteins
- GRK phosphorylation sites for receptor downregulation
What is a process of receptor inactivation?
-desensitization (block active receptors from turning on additional G proteins)
What is the process of desensitization?
- G protein coupled receptor kinase phosphorylation a GPCR
- Proteins called arrestins compete with G proteins to bind GPCRs
-GRK phosphorylates so that arrestin can bind and self regulate
What does adenylyl cyclase do?
- removes two phosphates as pyrophosphate
- converts AMP to cyclic AMP (to act as second messenger)
What does cAMP do?
Activates protein kinase A
Where does Protein kinase A phosphorylate on target proteins?
- serine
- threonine
What do kinases do?
Phosphorylate
What do phosphatases do?
-dephosphorylate
What does phosphorylation do?
-changes a proteins charge and generally leads to a conformation change which can alter ligand binding or other features of the protein resulting in an increase or decrease of its activity
What is required to activate enzyme coupled receptors?
-dimerization
What are enzyme coupled receptors?
-transmembrane proteins that bind ligands
What is an RTK?
- receptor tyrosine kinase
- receptor binds ligands and receptor is also tyrosine kinases
What is autophosphorylation?
When the tyrosine kinase from one monomer phosphorylates the tyrosine residues on the other identical monomer
What does Sos do? (In terms of Ras)
-displaces GDP for GTP on Ras activating it
Where is Ras located?
It is membrane bound
What is Src?
A non-receptor tyrosine kinase
A cytosolic kinase
What are the four Src domains?
- SH2
- SH3
- PTK (N-lobe)
- PTK (C-lobe)
Is every gene a proto-oncogene?
No, only those that can turn into a gain-of-function gene
What is an oncogene?
- when a normal gene mutates into a gain-of-function gene
- cancer gene
What is a proto-oncogene?
-a normal gene
What are v-Src and c-Src?
-c-Src would be considered the proto-oncogene that underwent mutations to become the oncogene (v-Src)
What domain interacts with Grb2 and sos?
SH2 domain
What is Ras?
- A small GTPase that is anchored at the inner surface of the plasma membrane
- mediates signaling by most RTKs
What activates Ras?
-the binding of the GEF (SOS)
How does Ras activate the MAP kinase signaling cascade?
By simply binding to RAF (MAP kinase kinase kinase)
What is constituitively active Ras?
-mutated Ras protein that hydrolyzes GTP very slowly
What do scaffold proteins do?
-help prevent cross-talk between parallel MAP kinase modules
What do TGFb (transforming growth factor b) receptors do?
-regulates many cell functions including cell proliferation, programmed cell death, specialization and key embryonic events
What is one thing that TGFb does?
-associates with receptor-regulated SMAD protein and phosphorylates it
What is one thing about cytokine receptors?
- stably associated with cytoplasmic tyrosine kinases (JAKS)
- JAKS phosphorylate STATS which migrate to the nucleus
What is one thing Wnt does?
-binds to Frizzled a 7 segment transmembrane receptor (not a GPCR because doesn’t bind to G proteins)
What is Hedgehog?
-a ligand
What are TNFa and TNFa receptor
- trimers
- important in the immune response
