Signal Transduction Part 1

Lecture 21

Cell signaling

process that cells communicate with one another, receive and respond to external cues, and coordinate their actions

they then bind to specific receptors on the surface of a target cell or inside it

cell signaling causes the release of signaling molecules

what then happens to these molecules?

1. signal reception

2. signal transduction

3. cellular response

Three primary steps of cell signaling

signal reception

binding of the signal molecule, or ligand, to a receptor on the cell surface

signal transduction

involves the activation of intracellular signaling molecules, often in the form of protein kinases

cellular response

once the signal has been transmitted intracellularly, it can have a variety of effects on the cell-specific response to a signal

cellular response

changes in gene expression, alterations in protein activity, cytoskeletal rearrangements, or changes in cellular metabolism

signal transduction

biological systems rely on complicated signaling mechanisms to provide organs and tissues with information on their correct function

signal transduction

a crucial part of cell signaling, focuses on chemical and physical signals transmitted within a cell after a signaling molecule binds to its receptor

signal transduction

results in a desired cellular response- cell type dependent

Cell A

pathway leads to a single response

response 1

Cell D

different receptor leads to a different response

response 5

Cell B

pathway branches, leading to two responses

response 2 and response 3

Cell C

cross talk occurs between two pathways

response 4

transmembrane proteins

polar signaling molecules bind to membrane receptors

intracellular signal

often uses second messengers

enzyme activation

cell movement

short term changes membrane receptors

altered DNA transcription

long term changes membrane receptors

extracellular signal

first messenger

second messengers

the molecules that carry on the message are called

hydrophilic second messengers

hydrophobic second messengers

a gaseous second messenger

What are the three signal transduction second messengers

G-protein coupled receptors

protein kinase receptors

two examples of membrane receptors

G Protein Coupled Receptors (GPCRs)

transmembrane proteins that interact with G protein

G proteins

GTP binding proteins

G proteins

peripheral membrane protein

trimers- a, B, and y subunits

a subunit binds GTP or GDP

GPCR and G Protein is inactive

GDP bound a subunit of the G protein

What happens if there is no signal in membrane receptors

ligand bound GPCR is activated

• conformation change

G protein is activated- a subunit releases GDP and binds to GTP

activated a subunit activates effector protein

B and y subunits can also activate other effector proteins

What happens when a signal is present in membrane receptors

membrane receptors

G protein coupled receptors

a subunit converts GTP to GDP (removal of one phosphate)

reassociates with GPCR and the B and y subunits

G-protein is inactive again

alpha subunit hydrolyzes GTP to GDP

beta and gamma subunit reassociate with the alpha subunit

How do you deactivate the signaling pathway of G protein

phosphorylation of glycogen synthase

join glucose molecules to form the energy storing molecule glycogen, thus preventing the storage of glucose as glycogen

phosphorylation of phosphorylase kinase

catalyzes the breakdown of glycogen, releasing glucose, which can then enter the bloodstream

kinase activity

can phosphorylate (attach a phosphate group) proteins

receptors can have

protein kinase receptors

ligand bound receptors dimerize

autophosphorylation

phosphorylation of target proteins: cells response, which includes the insertion of glucose transport proteins into the cell

mitogen- activated protein kinases (MAPKs)

A signal transduction cascade involving only proteins

Mitogen activated protein Kinases

activation of monomeric G proteins (only one subunit)

activation of MAPKS phosphorylate target proteins

• promote cell division

monomeric G proteins

are also active when bound to GTP

termination of signaling pathway

removal of internal signaling molecules

receptor recycling

removal of external signals

Termination of Signaling Pathway (removal of signaling molecule)

phosphatase inactivates a protein kinase

GTPase inactivates a G protein

phosphodiesterase inactivates cAMP

termination of signaling pathway (removal of signaling molecule)

external signals are removed:

• reuptake of neurotransmitters (recycling system)

• degradation of hormones

• ions are pumped out of the cytosol

endocytosis

endosome

lysosome

Three ways of receptor recycling

endocytosis

internalize membrane receptors

endosome

vesicle with internalized receptors

lysosomes

degrade internalized receptors (if needed)

on the cell surface

where are membrane receptors located?

inside the cell

where are intracellular receptors located?

on the cell membrane

where are adenosine receptors located?