Lecture 23 12/07/07 Cell Signaling and Signal Transduction
Cell Signaling –
How cells communicate with other cells and its environment
•
Local and long distance signaling
o
Local: paracrine + autocrine singaling
Paracrine – specifically when one cell secretes ligand, ligand is recognized
by neighboring cell.
Receptor is in close proximity but different cell types
Autocrine – when cell that is secreting and recognizing are the same cell
types within a tissue
o
Long: endocrine + synaptic
Endocrine – when cell produce a signal or ligand, signal is secreted into
circulatory system (blood or lymph) travel to distant location
Synaptic – neurons communicate with each other
electrical signal
recognized by another cell
neurotransmitter
•
Signaling functions within cell by signaling pathways
o
When ligand binds
Intracellular signal transduced inside cell
Ligand = 1
st
messenger
2
nd
messenger activated by receptor, not directly by
ligand
o
Example: adrenaline – ligand, 2
nd
messenger – cyclic AMP
capable of
activating other pathways in cell
•
G-protein Coupled Receptors (GPCR’s)
– large family of cell surface receptors
o
7 transmembrane domain containing proteins + 1 ligand binding domain
o
G-protein associated with these receptors (they are not small)
o
G-protein:
Heterotrimeric G-proteins
(3 subunits)
Cause activation of signal transduction cascade
α and γ subunits anchor into membrane by myristolated tail (14 C
saturated fatty acid tail)
Myristolated tails localize to lipid rafts and caveolae
G-protein attaches near where G-protein receptor will be when receptor is
not bound
Ligand acts as GEF
Ligand binds
Gα
GDP
GTP
Gα separates from Gβγ
Gα is more active, carry out more functions
Gβγ always stick together, act as one subunit
Both activate different downstream signaling events
How to shut off: hydrolyze Gα
GDP, Gα rebinds to Gβγ
return to
plasma membrane
Example:
How glucose is mobilized when adrenaline is produced and binds to cells in liver
Ligand (1
st
messenger) =
Adrenaline
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- Fall '06
- MEL
- cell biology, Cell Signaling, G-Protein Coupled Receptors, kinase kinase kinase, map kinase, MEK, MAP kinase cascade
-
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