Wordlists for Exam 3
Lectures 22, 24 & 25 -- Signaling - 1
Heterotrimeric G Proteins, cAMP, and Calcium

Surface receptors - generally water-soluble ligands
soluble proteins, peptides, amino acids, acetylcholine, etc.
(Some lipids)

Internal receptors - lipid-soluble ligands
steroid hormones, thyroid hormone, various lipids
Receptors have DNA-binding domains.

Surface Receptor types
ion-channel linked receptor = ligand-gated channel
enzyme-linked receptor = single pass membrane proteins
G-protein-linked receptors = seven pass membrane proteins

Signaling gasses

Ethylene (in plants)
NO, CO, H₂S

effector proteins = enzymesw, ion channels, other responders

"G proteins" = heterotrimeric G-proteins (alpha, beta, gamma subunits)
Nobel Prize 1994: Alfred Gilman & Martin Rodbell
G-protein-linked receptors = 7-passs proteins
Present in all eukaryotes.
Most abundant type of receptor in mammals -
more than 1000 genes in the human genome.
Multiple receptors with (slightly or vastly) different responses for same ligand:
9 epinephrine receptors
at least 5 receptors for acetyl choline
at least 15 receptors for serotonin
GTP binding to G protein = "On Switch"
GTPases - GTP hydrolysis = "Off Switch"

"2nd messenger" =

small intracellular mediator or
increase in cytosolic ion concentration

cAMP: cyclic 3',5'AMP

adenylyl cyclase: ATP => cyclic 3', 5'AMP
cAMP phosphodiesterase

kinase reaction

X-OH + ATP ---> X-O-P + ADP ( phosphorylation)

protein kinase reaction

Protein-OH + ATP ---> Protein-O-Phosphate (charge = -2) + ADP

phosphoprotein phosphatase ( = protein phosphatase) ( dephosphorylation)


protein kinase reaction = "on switch"
phosphoprotein phosphatase reaction = "off switch"

phosphoprotein phosphatase activity usually constitutive

-OH-containing AAs:

serine, threonine

serine/threonine protein kinases

tyrosine

tyrosine protein kinases

histidine protein kinases

Phospho-binding protein modules


Phosphotyrosine binding domains

SH2 domain
PTB domain

Phosphoserine/phosphothreonine binding protein

14-3-3 protein


cAMP dependent protein kinase = PKA = kinase A
A Kinase Anchoring Protein - "AKAP"
CREB = cAMP Response Element Binding Protein

G_S, alpha stimulates adenylyl cyclase
G_i, alpha - inhibits adenylyl cyclase
G_o, alpha - does not affect adenylyl cyclase
G_q, alpha - stimulates phospholipase C-beta

      alpha and beta-gamma from G_o also stimulate phospholipase C-beta

transducin -alpha subunit stimulates cGMP phosphodiesterase

Guanylyl cyclase activity in reproductive tissues activated by nitric oxide
type 5 CGMP phosphodiesterase in reproductive tissues inhibited by Viagra

calcium pulses
calmodulin (CaM) - 4 Ca²⁺ binding sites
CaM Kinase II

protein kinase G = kinase G = PKG

cyclic GMP (guanylyl cyclase)

TGF-beta = Transforming Growth Factor beta
MAP Kinase - activated by phosphorylation
phosphorylase kinase
protein kinase C = PKC = Kinase C


phospholipase C
PI(4,5)P₂ - phosphatidyl inositol (4,5) bisphosphate
IP₃ - Inositol 1, 4, 5 trisphosphate
DAG - diacyl glycerol
phosphatidyl serine (PS)

PI3 Kinase


PH (Pleckstrin homology) binding domains:

PI (3,4) bisphosphate
PI (3,4,5) trisphosphate

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