Cell Signaling Quiz One Flashcards
Three parts of a signaling pathway
Reception, transduction and response
Reception
Receptor binds signal
Transduction
Passing of message
Response
Some action taken by the cell
Sites of response in signaling pathways?
Nucleus, vesicles, cytoplasm, other bits of endomembrane system, PM, cytoskeleton
Different outcomes of signal molecules depend on different cell types.
Signaling molecule may activate multiple pathways
May act in concentration dependent manner
No signal: cell does X
Some signal: cell does Y
Lots of signal: cell does Z
What is the key to signaling?
Change
Change in concentration of intracellular signaling molecule (Ca2+, BMP, cAMP, cGMP, IP3, etc…)
Change in protein activity (activation/deactivation or increase/decrease in activity)
How do we get change in protein activity?
Conformational change and location
Examples in change in conformation of proteins?
Accessibility of active site
Dissociation from binding partner
Formation of higher-order complex
exposure of other regulating element
Degradation sequence exposure (leads to protein destruction)
Examples of change in protein activity location?
Nuclear import/export (nucleus vs. cytoplasm)
Membrane-bound vs. cytoplasmic
What is the key to signaling working properly?
Specificity
Signaling molecule binds receptor (right molecule binds the right receptor)
Transduction is specific
Outcome is specific
Characteristics of a signaling molecule?
Small (permeability and diffuses easily)
Lifespan requirements
Must be able to be released quickly (Can accomplish this with either 1. Synthesize, sequester, and release or 2. rapid synthesis
Therefore it is not a protein since transcription takes time.
Therefore is ither an ion or a molecule created by a catalytic reaction
How does the PKC and CaM-KII pathway get activated at the right time when they both need Ca2+ to work. How do they not activate one another when Ca2+ is present?
Scientists are not sure however:
Specific pathways have different molecules in specific areas of the cytoplasm
Therefore cytoarchitecture may play a role in this activity
Perhaps cytoplasm is compartmentalized
Signal molecules
Extracellular binders
Intracellular binders
Hormones
Part of the endocrine system
water soluble
small, hydrophilic, cannot cross PM
Histamine
mast cells, promotes blood vessel dilation
has a negative charge since it has an N2 on it
Epenephrine
Adrenal medulla
Rapid response when more energy is required
Has places for positive and negative charges
peptide hormones
vascular system
water soluble
vacuoles and secretory vesicles (get sent out and to exit cell space
Release is usually initiated by a Ca2+ spike (fastest way to do anything at all in signaling)
Insulin and glucagon
Insulin:
Most common peptide hormone
peptide synthesized as a pre-protein called proinsulin
Undergoes proteolytic cleavage to mature into insulin (It attaches to receptors on pancreas for the uptake of glucose)
A chain (22 A.A.)
B chain (30 A.A.)
Insulin function
Uptake of glucose
Lipid synthesis
Protein synthesis
Proliferation
Glucagon
Glycogen breakdown
Lipid hydrolysis
Increase in glycolysis
Increase in respiratory rates
Lipophilic Molecules
Some bind extracellular receptors
DONT cross PM (prostaglandins)
Arachidonic acid derivatives (20 carbons with 5 carbon ring)
9 classes
Some can pass the PM: Steroid hormones, thyroid hormones, retinoids
What is cholesterol derived from?
Steroids
Plant hormone
Auxin
Cytokines
Paracrine or autocrine signaling
Over 80 types
Generally released by immune cells
<10KDa –> ~70KDa
Most are 15-40 KDa
Interferons
Viral infections
NK cells make IF-gamma
Interleukins
IL-1 –> IL-38
Maturation process
Synthesized in pre=protein state
Are cleaved post translation
TNFs
Tumor necrosis factor
Monocytes and macrophages
Involved in cell survival and cell death
Proliferation and differentiation
TNF-alpha and TNF-beta
Bind same receptor
TNF-beta brings in additional protein to form a trimer to cause a different signal than TNF-alpha
CSFs
Colony stimulating factors
Development of bone marrow
Induces development of leukocytes
Athenian cells, fibroblasts, etc…
Uptake of CSFs in response to infection
Chemokines
~45 types
Structurally related
Not functionally related
Growth factors
Proliferation/differentiation
Over 50 types of GFs
14+ families of receptor
PDGF
Platelet derived growth factor
AA, AB, BB attached to PDGF
Most studied growth factor of all?
EGF
EGF
Contain cysteine rich domain
6 cysteines in it
held together by disulfide bridges
Therefore very stable structure
hydrophobic regions on surface of EGF molecules
FGF
Mammals: GFG-a, FGF-b, FGF3-19
Humans DO NOT have FGF-15
Also key for locomotion
Neurotransmitters
Small molecules:
GABA (acetylcholine)
dopamine
signal across synapse (20nm)
Neuropeptides:
Beta-endorphin (vasopressor)
Some other small molecules e.g., ATP
GPCR
G-protein coupled receptor
gamma and alpha are membrane bound
alpha holds a guanine nucleotide
Signal molecule binds GPCR which causes conformational change
Shift in loop causes nucleotide change in G-alpha
Leads to dissociation of G-alpha from G-beta/gamma
800-1,000 types
Three subfamilies of GPCR
A, B and C
B downstream uses cAMP
Ion channels (Gated ion channels)
Acetylcholine receptor:
6 subunits
2 alpha subunits
1 beta subunit
1 gamma subunit
1 delta subunit
Glutamate receptor:
four subunits, many possible combos
Ligand binds alpha
18 genes with splice variants
Enzyme-linked receptors
Enzyme linked or enzyme associated with them
many dimerize to activate
N-terminus is always extracellular
Only one TM domain
Binding between signal + receptor
Reversible reaction L+R –> LR
<–
Kd
Dissociation constant
State at which receptors are 1/2 bound and 1/2 unbound
Low Kd = high affinity L –> R
High Kd = low affinity L –> R
Kd equation
Kd= ([R] [L])/[RL]
Do we want a high Kd?
Depends!
Consider:
1. Signal molecule concentration
2. number of signal receptors on the cell
