Chapter 3 Flashcards
What are 3 methods of cell-cell communication?
- Endocrine
- Paracrine
- Autocrine
Define hormone:
Chemical substance that is released into the blood to create an effect somewhere else.
What are the 4 types of signalling molecules?
- Amines (tyrosines)
- Peptides
- Steroids
- Small molecules (amino acids, nucleotides, ions, and gases).
How do extracellular signals interact with target cells?
They bind to their receptors located either on the membrane or in the intracellular fluid.
What are the 4 types of receptors?
- Ligand-gated receptors
- G-protein coupled receptors
- Catalytic receptors
- Nuclear receptors
Define catalytic receptor:
When activated by its ligand, these integral membrane receptors go on to act as an enzyme or as part of an enzymatic complex.
What are cadherins?
Extracellular domains of transmembrane receptors
How do adherens junctions form?
When cadherins interact with each other. Dependent on Ca2+.
What are catenins?
Intracellular proteins that cluster when cadherins between the two cells interact with each other. These clusters allow for the actin cytoskeleton to attach to the catenins for structural support.
What are tight junctions?
Transmembrane proteins that link with other transmembrane receptors on different cells. Prevent water transport.
Explain what an membrane-associated ligand is.
When a receptor on a cell binds to another receptor on a different cell to initiate a response. Important in developmental influence of cell fate.
What is the role of second-messenger systems?
To amplify signals and integrate responses from different sources.
What are G-proteins?
Heterotrimeric proteins in some combination of alpha, beta, and gamma subunits
What does PDE (phosphodiesterase) do?
Converts cAMP back to ATP.
What activates PLC?
Ga
What does PLC activate?
PIP2
Once activated, what does PIP2 do?
Dissociate into IP3 and DAG
What does DAG do?
Activate PKC (protein kinase C)
What does IP3 do?
Signals the release of Ca2+ from the ER
What are receptor tyrosine phosphatases required for?
Lymphocyte activation
What are pY Motifs recognized by?
SH2 and SH3 domains
What do receptor tyrosine kinases create?
Phosphatyrosine motifs (recognized by SH domains of downstream effectors)
Serine and threonine kinases can also act as?
Catalytic receptors
What is the difference between receptor guanylyl cyclase vs. soluble guanylyl cyclase?
Receptor guanylyl cyclases are activated by ANP (atrial naturetic peptide) while soluble guanylyl cyclases is activated by nitric oxide (NO).
What do receptor guanylyl cyclases specifically do?
Convert GTP to cGMP
What do receptor serine/threonine kinases do?
Phosphorylate proteins that have serine/threonine residues
What do receptor tyrosine kinases do?
Phosphorylate themselves as well as proteins that have tyrosine residues
What do tyrosine-kinase associated proteins do?
Phosphorylates cytosolic (non-membrane bound) tyrosine kinase
What do receptor tyrosine phosphatases do?
De-phosphorylates tyrosine residues from proteins
What are the 5 receptors that are catalytic?
- Receptor guanylyl cyclases
- Receptor serine/threonine kinases
- Receptor tyrosine kinases
- Tyrosine-kinase associated receptors
- Receptor tyrosine phosphatases
What is platelet-activating factor?
A lipid mediator that is unrelated to arachidonic acid
How do you terminate eicosanoids?
Degrade them!
What do HETEs and EETs (epoxygenase products) do?
Increase release of Ca2+ from internal storages and increase cellular proliferation
What do leukotrienes do?
Play a major role in inflammation
What do prostaglandins, prostacyclins, and thromboxanes do?
- Are vasoactive
- Regulate platelet action
- Regulate ion transport
How are eicosanoids formed?
Through cyclooxygenases, lipoxygenases, and epoxygenases
What enzyme releases arachidonic acid?
Phospholipase A2
What activates PKC (protein kinase C)
DAG (diacylglycerol) and Ca2+
How are calmodulin-dependent kinases activated?
Ca2+
What enzyme is antagonistic to kinases?
Phosphatases
What enzyme is antagonistic to phosphatases?
Kinases
What does cAMP do?
Activate PKA (protein kinase A)
Which terminus is in the extracellular fluid of a 7-transmembrane receptor?
N-terminus
Which terminus is in the intracellular fluid of a 7-transmembrane receptor?
C-terminus
Which domain of a 7-transmembrane receptor do G-proteins bind to?
5-6 intracellular loop.
How does Ga-GTP go to Ga-GDP?
Intrinsic activity of Ga
What happens once Ga-GTP goes to Ga-GDP?
Ga reassembles with Gb and Gy to re-form the heterotrimeric G-protein
What happens to cGMP-dependent channels once cGMP is degraded in the cell?
They close!
What is PKA made of?
PKA is consisted of 2 regulatory subunits and 2 catalytic subunits
What happens once PKA is activated by cAMP?
The 2 catalytic subunits dissociate and are free to phosphorylate other proteins
How many Ca2+ ions bind to calmodulin?
4
What does calmodulin do once activated?
Activate other proteins
What activates calmodulin?
4 Ca2+ ions
Where is arachidonic ALWAYS found?
One the second carbon of the glycerol backbone of a phospholipid
What are the two remnants of the phospholipid after it is cleaved by phospholipase A2?
Arachidonic acid and lysophospholipid
Which catalytic receptor contains carbohydrate sugar groups located on its extracellular domain?
Tyrosine phosphatase receptors.
What does RTK stand for?
Receptor tyrosine kinase
List the 10 steps of the MAPK pathway:
- Ligand binding causes receptor tyrosine kinase dimerization
- RTK phosphorylates itself
- GRB2 (with an SH2 domain that detects the phosphorylation) is activated by the phosphorylated RTK
- SOS then binds to GRB2 and is activated
- SOS then activates Ras by exchanging GDP for GTP
- Ras then activates Raf-1 by binding to it
- Raf-1 then activates MEK by phosphorylation
- MEK then activates MAPK by phosphorylation
- MAPK phosphorylates many other proteins
- MAPK translocates to the nucleus and phosphorylates transcription factors.
