Where do singals come from
a. synaptic signalling
Protein-protein interactions can be what??
Propagation of signal from one molecule to another mediated via conformational changes from ??
1. Allosteric effects
2. Covalent Modification (ex. phosphorylation)
: protein-protein interactions
How does signaling lead to a change in cellular behavior?
Change expression of genes
Change activity of cellular enzymes/proteins
What are the Main types of Transmembrane Receptors??
G-Protein coupled receptors (GPCRS, 7TMs)
Channel-linked receptors ligand-gated channels are used where ? and Common in??
Used in many cell types
Common in nervous system responses
type of enyme commonly involved in signal transduction
What are the types of kinases
Another enzyme type commonly involved in signal trandsuction
Receptor Tyrosine Kinases (RTKs) are found in what??q
What happens with insulin in Pathway 1??
increased protein translation Glycogen/Lipid synthesis glucose uptake
What happens with insulin in pathway 2
increased transcription (genes important for cell division)
First kinase (Ras activates MKKK)
Second kinase (MKKK plus 3 P)
MAP kinase (activation of MK w/3P)
Response (cellular response)
What is Ras
What does Ras do ??
Small GTP binding protein
Active when bound to STP
Can bind to other proteins and cause conformational change
Mutated in many cancers
RTK inactivation are
Protein tyrosin phosphatase (PTP)
What happens to the G-Protein coupled receptors (GPCRs)
Ligand binds--> heterotrimeric G protein binds GTP ---> effector protein activated ---> second messenger system activated
diffusible small molecules or ions generated or released in response to enzyme activity in signaling pathways
Examples of effector proteins
Adenylyl cyclase (cAMP)
Inositol trisphoshate (IP3)
Adenyly Cyclase Generates
Cyclic AMP (cAMP)
Example of Adenylate Cyclase Regulation
what does Hydrolysis of cAMP do ?
Phospholipase C is the generation of
DAG and IP3
IP3---> Ca++ Release from ER DAG ---> ______??
Protein Kinase C activation
What are the Main types of intracellular Receptors??
Steroid Hormone Receptors
Thyroid Hormone Receptors
Nitric Oxide Signaling
What happens when there is Nitric Oxide (NO)?
Calcium Release------> Smooth Muscle Contraction
What are examples of Second Messengers
cyclic nucleotides (ex. cAMP and cGMP)
inositol trisphosphate (IP3) and diacylglycerol (DAG)
calcium ions (Ca2+)
How can two cells respond differently to the same signal??
Different receptors can activate ______ _______
glucose beeded because of low blood sugar ---> breakdown gylcogen
glucose needed to escape -----> breakdown gylcogen
What is down to Turn off Signaling Pathway??
Internalization of receptor
Hydrolysis of GTP ---> GDP
Destruction of 2nd messengers
-cAMP, cGMP (phosphodiesterase)
What is the Signaling Process?
1. Signal sent
2. Receptor/ligand binding---> conformational change
3. Transduction (amplification via 2nd messengers, kinase cascade)
4. Cellular response (change in protein activity, gene expression)
5. Removal of signal
bio exam2 ch9