Cell Signaling

Importance

The survival of an organism depends largely on its ability to receive and respond to stimuli such as chemicals, odors, light and sound, also cell damaging agents and pathogens from the
environment

Dead cells - apoptotic cell
•cell death to prevent damage carry on

Short d

Intracellular signal receptors

Three stages in cell signaling

local regulators(endocrine system) travel only short distance

Paracrine Signaling
secreting cell produce secretory vesicle and local regulator diffuse through extracellular fluid.

Synaptic Signaling
•Electrical signal along nerve cell triggers release of neurotransmitter.
•Neurotransmitter diffuse across synapse.
•Target cell is stimulated

Long d

• Most often, the ability of a cell to respond to a signal depends on the presence of a specific receptor.
• Each cell displays a variety of receptors that allow it to respond
to a corresponding set of signals

endocrine cell secrete hormone into blood stream and travels to target cell specifically binds hormone.
• Pancreases secrete insulin to liver in specific receptor
• one cell type can have different receptor

Reception
•Binding between a signal molecule and receptor is highly specific
(most signal molecuels are plasma membrane perotein

Transduction
relay molecules in a signal transduction
pathway
•A structural change in a receptor often initiates signal transduction

Response
•activation of cellcular response

•found in cytosol or nucleus
•Hydrophobic signal molecules(e.g. steroid and thyroid hormones) can readily cross the membrane and activate receptors

1) Extracellular fluid pass through plasma membrane
2) bind on receptor protein to become Hormone-receptor complex
3)The complex goes into the nucleus and bind on DNA
4)Give response to produce mRNA
5)mRNA binds on ribosome to produce new protein

•An activated hormone-receptor complex can act as a transcription factor, activating transcription of specific gene(s)

Cell surface receptors

Ion channel receptor
(pumping ion in or out)
(controlled by signal molecules)

G protein linked receptor
•G protein will have structural change
Both G protein and enzyme will be activated

Receptors tyrosine kinase
Signal molecule in form of a dimer to active catalytic domain

•Sensory(light/taste/smell) and hormone receptors

~1000 GPCR in human
200 functionally known
600 orphan GPCRs(unknown)

~50% drugs in the market act by binding to GPCRs

Adrenaline
•Secreted by adrenal glands
•Actions of adrenaline need β2 adrenergic receptor (GPCR)
•Response of target cells:increase energy production and heart rate

• Binding of signaling molecule activates GPCR to interact with an inactive G protein. When GTP is bound, G protein is now activated and have structural change.
• Activated G protein leaves GPCR and binds to an enzyme for cellular response.
• G protein hydrolyzes GTP to GDP and becomes inactivated.
it then leaves and enzyme and returns to its original state

• receptors that attach phosphates to tyrosines
• can trigger multiple signal transduction pathways at once
• Abnormal function of receptors often associated with cancers,

e.g. epidermal growth factor receptor (EGFR) –
mutations are
associated to lung cancer
(RTK is mutated becomes keep activated state always)

1) Singaling molecule bind on Ligand-binding site on tyrosine(inactivated RTK monomers


2) two monomers join together to form dimer
(only partically activated)


3) 6 ATP change to 6ADP and unphosphorylated dimer become fully activated RTK (phosphorylated)


4)Activated relay proteins become inactive relay proteins when producing multiple cellcular responses

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