Lecture 23 12 - /07/07 Cell Signaling and Signal...

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
 When Adrenaline binds, cell wants to make more glucose