Lecture 8 Flashcards
Paracrine signaling
Signal acts on a neighboring cell (NO2)
Endocrine signaling
Transported through circulation to target cell (hormones)
Autocrine signaling
Cell responds to its own signal
Neurotransmitter
Type of paracrine signaling
Bind to membrane receptors on cell surface
What are examples of neurotransmitters?
Ach
Amino Acids (Glu, Asp, Gly)
GABA
Monoamines
What are the two types of monoamines?
Catecholamines (dopamine, norepinephrine, epinephrine)
Indoleamine (serotonin)
What are examples of non-neurotransmitters?
Insulin, Glucagon, Pituitary Trophic Hormones
What are examples of growth factors?
Nerve, epidermal, and platelet-derived growth factor
What type of messengers bind extracellularly?
Neurotransmitters
Non-neurotransmitters
Growth factors
What messengers bind intracellularly?
Steroids
Non-steroids
What are examples of steroids?
Testosterone
Estrogen
Progesterone
Corticosteroids
What are examples of non-steroids?
Thyroid hormone
Vitamin D3
Retinoids
What are the different receptor classes?
G protein-coupled receptors
Tyrosine kinase receptors
Cytokine receptors
What are the characteristics of G protein-coupled receptors?
7 membrane-spanning helices NH2 is extracellular and binds to ligand COOH is intracellular and interacts with G protein Heterotrimeric (alpha, beta, gamma) Alpha interacts with G protein
What are the functions of G protein-coupled receptors?
Regulate enzyme/ion channels
Largest family responsible for odor detection
Control effectors altering activity of second messengers (cAMP, DAG)
When a ligand binds to a G protein-coupled receptor, what happens intracellularly?
GDP is exchanged for GTP on alpha subunit
Alpha subunit breaks away from Beta/Gamma dimer
Alpha subunit acs on effectors or activates other G proteins to amplify signal
Effector stimulates GTPase activity of alpha subunit
How does an alpha subunit for G protein get activated?
A GDP is exchanged for a GTP resulting in activation
What are the characteristics of enzyme-linked receptors?
Single pass transmembrane proteins
Associated with intracellular effector capable of generating intracellular signal
C-terminal undergoes ligand-induced dimerization & receptor autophosphorylation
What are the classes of enzyme-linked receptors?
Guanylyl cyclase activity receptors (increase intracellular [cGMP])
Phosphorylation/dephosphorylation catalysts for intracellular signaling proteins
What are the characteristics of tyrosine kinases?
Phosphorylation of tyrosine in catalytic domain increase protein kinase activity
Phosphorylation of tyrosine out of catalytic domain creates binding sites for other proteins that transmit signals downstream (amplifies incoming signal)
What are the characteristics of cytokine receptors?
No cytosolic catalytic activity
Associated with JAK
Can’t autophosphorylate
What are characteristics of non-receptor protein-tyrosine kinases?
Belong to JAK and Src families
Ligand binding induces dimerization
Dimerization of receptor leads to dimerization of JAK’s which autophosphorylate and then phosphorylate the receptor
Phosphorylation of receptor provides binding sites for recruitment of downstream signaling molecules (STAT’s)
What are characteristics of the cAMP pathway?
ATP converted to cAMP
cAMP degraded to AMP
cAMP binds to cAMP dependent protein kinase (Kinase A)
Kinase A moves into nucleus
Kinase A binds to CREB (transcription factor) which is bound to CRE (cAMP response element)
Turns on specific genes dependent on transcription factor involved
Describe the JAK-STAT pathway
JAK’s activate when cytokine receptors dimerize, then JAK’s come together and autophosphorylate
(These JAK’s phosphorylate receptors)
Receptors have binding sites for STAT’s
STAT is phosphorylated by JAK and forms dimer which translocates into nucleus and activates transcription
T/F: All STAT dimers activate the same DNA sequences
False, different STAT dimers activate different DNA sequences
Describe the ERK-MAP kinase pathway
Ligand binds to membrane growth factor
Ras replaces GDP with GTP and interacts with Raf kinase
Raf phosphorylates and activates MEK
MEK activates MAPK(ERK) which moves into nucleus and phosphorylates Elk-1 (transcription factor)
What are characteristics of hedgehog pathway?
Receptor is transmembrane protein called “Patched”
Inhibits a second transmembrane protein called “Smoothened”
What does the hedgehog pathway play important role in?
Determination of cell fate during embryonic development
Regulation of proliferation of stem cells into adult tissues
Describe the hedgehog pathway
Binding of hedgehog inhibits “Patched”
Inhibition of “Patched” leads to activation of “Smoothened” and activation of transcription from Gli
Describe the Wnt proteins
Growth factors
Bind to receptors of Frizzled and LRP families
Signals from Frizzled and LRP stabilize beta-catenin which is a transcriptional activator
Describe the notch pathway
Cell-cell interaction during development (paracrine)
Single transmembrane domain
Ligand binding leads to proteolytic cleavage of notch
Intracellular domain moves into nucleus and converts transcription factor CSL from repressor to activator
