Signaling Flashcards
(26 cards)
Ligands (primary messengers):
hormones (insulin, glucagon), growth factors, proteins, small molecules (histamine or epinephrine)
Receptors:
Tyrosine kinase/phosphatase receptors
G protein-coupled receptors (GPCR)
G proteins (transduction):
Heterotrimeric (3 subunits)
Monomeric (1 subunit)
Effectors & 2nd messengers (transduction):
Effectors are usually proteins
2nd Messengers usually small mol like calcium, IP3, DAG, etc.
Ligands (Agonists)
small molecules that bind to specific receptors. Variety of shapes and sizes.
Membrane Receptor Types
G protein-coupled receptors (GPCR); aka
7TMR, serpentine receptors & RTK RTP
G protein-coupled receptors (GPCRs)
Epinephrine, Insulin
Receptor Tyrosine Kinases (RTKs)
Epidermal Growth Factor
Physiological Responses Downstream of GPCRs
Cell growth and differentiation
RTKs (Glucose met.,Cell growth)
GPCRs Bind Ligands Within
the TM Domains
“Infamous” GPCR Drugs and Agonists
Heroin, Morphine:m-Opioid Receptor
(endorphins)
LSD:5-HT Receptor (Serotonin)
THC:CB1, CB2 (Cannabinoid) Receptors
Agonists
ligands that directly bind GPCRs
and stimulate a physiological response that is beneficial for the patient. e.g. albuterol (bAR, asthma), THC (CB1-2), etc.
Antagonist
ligands that also directly bind GPCRs but do not stimulate a response. This class works by competing with endogenous ligands e.g. antihistamines, b-blockers, curare (nicotinic acetylcholine receptor), clozapine (dopamine receptors) and caffeine (A2 adenosine receptor).
G Proteins (GTPases)
So named because they bind guanyl nucleotides
Heterotrimeric
(3 subunits: a, b, g),
defined by the a subunit families:
4 = Gai, Gas, Gaq, & Ga12/13
Monomeric (1 subunit related to Ga)
Ras (rat sarcoma)
Heterotrimeric G Protein Quaternary Structure
A ribbon diagram shows the relation between the three subunits. In this complex, the α subunit (gray and purple) is bound to GDP. Notice that GDP is bound in a pocket close to the surface at which the α subunit interacts with the βγ dimer. (B) A schematic representation of the heterotrimeric G protein
Heterotrimeric G Proteins Directly Contact
GPCRs
Membrane localization
a and g subunits are lipid modified
Effectors (Targets of G Proteins)
Adenylate cyclases
(downstream of Gas)
Phospholipases (PLCb is downstream of Gaq and bg)
Adenylate Cyclase is Stimulated by
G alpha s
Common 2nd Messengers
IP3 and DAG
Phospholipase C (PLC) Cleaves
PIP2 to generate IP3 and DAG
EF Hands are Protein Domains that Bind
Ca++
