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Where do singals come from
- Contact dependent
- Autocrin Signaling
- Paracrine Signaling
- a. synaptic signalling
- Endocrine Signaling
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)
- 3. Proximity: 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??
- Channel-linked receptors
- Enzymatic 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
- tyrosine kinases
- serine/threonin 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)
- activator (Ras)
- First kinase (Ras activates MKKK)
- Second kinase (MKKK plus 3 P)
- MAP kinase (activation of MK w/3P)
- Response proteins
- Response (cellular response)
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)
- Phosphlipase C
- Diacylglyerol (DAG)
- 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
- Dephosphorylation (phosphatase)
- Hydrolysis of GTP ---> GDP
- Destruction of 2nd messengers
- -cAMP, cGMP (phosphodiesterase)
- -Ca++ (re-sequestration)
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