Term
| Describe the modes of cell-signaling |
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Definition
1. Direct cell-cell: direct contact to neighbor
ex. integrins and cadherins
2. Secreted molecules
a. endocrine- hormones are carried in circulation to distant sites (estrogen)
b. paracrine- molecules act on neighboring cells (neurotransmitters)
c. autocrine- signal molecules act on themselves (T cells) |
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Term
| Describe Intracellular Receptors |
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Definition
-respond to signal molecules that diffuse across membrane (hydrophobic)
-bind in cytosol or nucleus
Types: steroids, thyroid, vitamin D, retinoic acid
Ex. TFs |
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Term
Describe Steroid Hormones
1. Sex
2. Corticoids
3. Others |
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Definition
*all derived from cholesterol
1. Sex- test, estro, progesterone
-all come from gonads
2. Corticosteroids- come from adrenal gland
a. glucocorticoids- stimulate glucose
b. mineralocorticoids- act on kidney to regulate salt and water balance
3. Thyroid-synthesize from tyrosine in thyroid; development and metabolism
Vitamin D3- regulate calcium metabolism and bone growth
Retinoic acid-synthesized from vitamin A; development |
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Term
| Describe Steroid Hormone Receptors |
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Definition
Nuclear receptor superfamily
-TFs that have domains for ligand binding, DNA binding, and transcript activation
-ligand binding to steroids regulate function as activator or repressor |
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Term
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Definition
-paracrine signal molecule in nervous, immune and circulatory systems
-alters activity of enzymes
1. synthesized from arginine by NOS
2. extremely unstable (t1/2= few seconds) so it acts locally
3. Effects: dilation of blood vessels
a. neurotransmitters from nerve cells stimulate NO synthesis by endothelial cells
b. NO diffuses to smooth muscle
c. activates guanylyl cycle which makes cGMP to induce muscle relaxation and dilation |
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Term
Describe neurotransmitters
1. Function
2. Structure
3. Pathway
4. Receptors |
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Definition
1. carry signals from neurons to neurons or other cells
2. hydrophilic molecules
-can't cross membrane
3. release is triggered by action potential
-neuros diffuse across synaptic cleft
-bind to receptors on cell surface
4. can't cross membrane so they bind to receptors
-many receptors are ligand gated channels which open in response to neurons |
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Term
Describe the following neurotransmitters
1. Acetylcholine
2. Dopamine
3. Epinephrine
4. Serotonin
5. Histamine
6. GABA |
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Definition
1. skeletal muscle contraction
2. HAPPY
3. adrenalin
4. relaxation
5. inflammatory response
6. suppress neural impulse |
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Term
Describe Peptide Signaling
1. Pep hormones
2. Neuropeptides
3. Growth Factors |
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Definition
*cannot cross membrane
1. proteins that act as hormones
ex. insulin, glucagon, pituitary gland
2. secreted by neurons that act as neurotrans
ex. endorphins and enkephalins decrease pain
3. used for animal cell growth and differentiation |
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Term
Describe the following Peptide Growth Factors
1. NGF
2. EGF
3. PDGF |
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Definition
1. nerve GF- regulates development and survival of neurons
-without NGF, apoptosis
2. epidermal GF- stimulates cell proliferation
3. platelet-derived GF- necessary to stimulate growth of damaged tissue |
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Term
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Definition
1. lipid signaling molecules
2. breakdown very quickly
-autocrine or paracrine
3. synthesized from arachidonic acid |
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Term
Describe G proteins
1. Structure
2. Function |
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Definition
1. 7 transmembrane alpha helices
beta/gamma subunit: bind to transmembrane portion
alpha: binds GDP or GTP and is released
2. alpha can activate different types of proteins
-adenylyl cyclase |
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Term
| Describe G coupled protein pathway |
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Definition
1. hormone binds to transmembrane G receptor
2. conformational change that allows alpha to bind to GTP
3. alpha bound to GTP dissociates from beta/gamma
*remains active with GTP and can signal more than one molecule until hydrolyzed
4. activates target downstream
ex. Epinephrine-> adenylyl cyclase converts to cAMP |
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Term
Describe the following G coupled protein pathways
1. Epinephrine
2. Heart muscle
3. Pertussis |
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Definition
1. activates cAMP -> glycogen to glucose
2. alpha subunit inhibits adenylyl cyclase
-beta/gamma open K channels to slow heart
3. toxin keeps GTP signal on so signal does not turn off |
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Term
| Describe caffeine and cAMP |
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Definition
-inhibits cAMP breakdown-> more energy
-phosphodiesterases break down cAMP
-over time, body makes more phosphodiesterases to maintain adequate cAMP levels |
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Term
Describe protein tyrosine kinases (TRK)
1. Structure
2. Function |
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Definition
1. N terminal ligand binding doman, single transmembrane alpha helix, cytosolic C domain with tyrosine kinase activity
2. phospho substrates at tyrosine
ex. growth factors (EGF, NGF, PDGF) and insulin |
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Term
Describe protein tyrosine kinases
Pathway |
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Definition
1. ligand induced receptor dimzerization
2. two peptides in cytosol authophospho each other
a. within catalytic domain, increases protein kinase activity
b. outside domain, creates binding sites for additional proteins |
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Term
| Describe protein tyrosine phosphatases |
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Definition
1. remove phosphate groups to counter act kinases
2. some work to activate
ex. CD45 on T and B cells |
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Term
| Describe a protein serine/threonine receptor kinase |
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Definition
TGF beta receptors
-control cell proliferation and differentiation |
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Term
Describe protein tyrosine kinases (TRK)
1. Structure
2. Function |
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Definition
1. N terminal ligand binding doman, single transmembrane alpha helix, cytosolic C domain with tyrosine kinase activity
2. phospho substrates at tyrosine
ex. growth factors (EGF, NGF, PDGF) and insulin |
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Term
Describe protein tyrosine kinases
Pathway |
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Definition
1. ligand induced receptor dimzerization
2. two peptides in cytosol authophospho each other
a. within catalytic domain, increases protein kinase activity
b. outside domain, creates binding sites for additional proteins |
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Term
| Describe protein tyrosine phosphatases |
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Definition
1. remove phosphate groups to counter act kinases
2. some work to activate
ex. CD45 on T and B cells |
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Term
| Describe a protein serine/threonine receptor kinase |
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Definition
TGF beta receptors
-control cell proliferation and differentiation |
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Term
Describe cAMP Pathway
1. Formation
2. Breakdown |
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Definition
*second messenger
1. from ATP by adenylyl cyclase
2. degraded to AMP by cAMP phosphodiesterase |
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Term
Describe cAMP Pathway
Protein Kinase A |
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Definition
Inactive- two reg and two catalytic subunits
-cAMP binds to regulatory unit to free catalytic (4 cAMP)
-free units can phospho serine residues
*dephospho by protein phosphatase 1 |
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Term
| Describe the function of Protein Kinase A with glycogen |
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Definition
1. Phoshporylase kinase is activated by phospho
-phosphos glycogen phosphoyrlase which converts glycogen to glucose
2. glycogen synthease is inactivated by phospho
*glycogen breakdown stimulated and glycogen synthesis is stopped |
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Term
| Describe Signal Amplification |
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Definition
1. each molecule of epi activates one receptor
2. each receptor may activate up to 100 molecules of Gs
3. Gs can stimulate many adenylyl cyclase
4. produce many cAMP
5. each protein kinase A phosphos many phosphrylase kinase and so on |
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Term
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Definition
cAMP response element
-regulatory sequence in genes
1. protein kinase A enters nucleus and activates CREB
2. CREB acts as TF for genes with CRE
CREB- memory; reset during REM sleep |
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Term
| Describe function of cAMP in odor receptors |
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Definition
1. odor causes G coupled protein to release alpha subunit
2. stimulates adenylyl cyclase to make cAMP
3. cAMP opens Na channels leading to nerve impulse
4. odor sensed in brain |
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Term
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Definition
functions in similar manner to cAMP a
-second messenger
-formed by guanylyl cyclase
-mediates blood vessel dilation through activation by NO or CO |
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Term
| Describe the role of cGMP in vision |
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Definition
1. photon hits retinal and changes it from the cis to trans conformation
2. this changes conformation of rhodopsin
3. rhodopsin activates G protein Transducin
4. alpha subunit stimulate cGMP phosphodiesterase
-decreases cGMP levels
5. creates nerve impulse through ion channels |
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Term
| Describe the relationship of cGMP and Na channels |
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Definition
*cGMP opens Na
1. in the dark, cGMP is present and keeps Na open
-depolarized and neuros are released
2. in light, cGMP is degraded and Na closes
-polarized and neurotransmitters stop |
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Term
| Describe role of Na and Ca channels |
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Definition
Light closes Na channels
-Na is permeable to Ca so Ca decreases in light as well
1. Low Ca stimulates guanylyl cyclase
2. cGMP is produced -> opens channel |
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Term
| Describe the PIP2 signaling pathway- IP3 |
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Definition
*located in the inner plasma membrane
1. PIP2 cleaved by phospholipase C (PLC)
-creates DAG and IP3
2. IP3 triggers release of Ca from ER
3. DAG activates Protein Kinase C
-PKC needs Ca release from IP3
-PKC serine/threonine kinase |
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Term
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Definition
Phospholipase C
1. PLC-beta
-stimulated by G proteins
2. PLC-gamma
-SH2 domain that associates with tyrosine kinase
-phospho increasing activity to hydrolyze PIP2 |
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Term
| Describe Calmodulin and CaM kinase |
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Definition
1. Calmodulin activated when Ca concentration increases
2. CaM kinases are activated by Calmodulin
-phospho metabolic enzymes, ion channels, TFs
-CaM phospho CREB (also activated by PKA) |
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Term
| Describe the PIP2 signaling pathway- PIP3 |
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Definition
1. PIP2 is phosphorylated by PI3 kinase
-yields PIP3
2. PIP3 targets Akt and PDK1
-Akt= PKB (ser/threo)
3. Akt also requires mTOR2
-mTOR is stimulated by growth factors
4. Akt phospho FOXO
-inactivates FOXO
-FOXO induces cell death |
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Term
Describe Akt
1. Requirements for activation
2. Targets |
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Definition
1. PIP3, PDK1, mTOR
2. proteins, TFs, protein kinases
-glycogen synthase kinase
-specifically FOXO by inactivating it
-FOXO leads to cell death |
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Term
| Describe activation of FAK |
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Definition
1. integrins bind to ECM
2. phosphorylates FAK
-protein tyrosine kinase
3. provides binding site for signaling molecules
-PLC-gamma, PI3 kinase, Ras |
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