Exam 2 Flashcards
The type of intercellular signaling in which one cell can communicate with another over long distances is called ___________.
endocrine
Describe autocrine signaling
one cell type is both the sender and the target
Which type of signaling is contact dependent?
juxtacrine
Synaptic signaling is a type of paracrine signaling used by __________.
nerve cells
In _________ signaling, the cells are in immediate vicinity of eachother.
paracrine
Describe intracellular receptors (4)
- usually bind hydrophobic ligands
- may be located either in the cytosol or nucleus in unbound state
- when bound to their ligand, regulate gene transcription
- when bound to their ligand, function as dimeric complexes binding to specific DNA sequences
Describe 3 functions of cell surface receptors
- when bounds to its ligand, could result in activation of an enzymatic cascade
- always opens an ion channel when bounds to its ligand
- must produce a second messenger when it binds to its ligand
Describe 3 methods in which cells can terminate signal transduction by cell surface receptors
- reducing agonist availability in the vicinity of the target cell
- internalizing and degrading the receptor-agonist complex
- modifying the receptor so that it is inactive or desensitized
What is calmodulin?
a protein that binds Ca2+
What are 4 downstream effects of the activation of phospholipase C?
- increase in intracellular Ca2+ concentration
- release of diacylglycerol (DAG) from a phospholipid
- activation of protein kinase C
- phosphorylation of certain cytoplasmic proteins
The a-subunit of G proteins may be ___________ because it has two forms.
- stimulatory or inhibitory
- Which form is released depends on the specific hormone and receptor that have interacted.
How can you increase cyclic AMP?
activate adenylate cyclase by a-subunit of Gs protein
Why would low GTPase activity result in constitutive activation of Gs and adenylate cyclase?
The GTP-bound a-subunit does not reform the aBy trimer.
Describe tyrosine kinases
- The N-terminal end is extracellular and site of binding of the ligand
- The catalytic site must be on an intracellular domain
- Dimerization causes causes its activation
- Growth factor binding to the receptor triggers dimerization which activates the kinase activity
- The first protein phosphorylated is the receptor itself, which then attracts other proteins to be phosphorylated
Ras protein is a critical regulator in cell proliferation, and its activity is enhanced by activated tyrosine kinase. Describe its action.
- adaptor proteins binding to phosphorylated tyrosines on receptor tyrosine kinase
- recruitment and stimulation of Ras-activating protein
- exchange of GDP for GTP on the Ras protein
- initiation of a cascade in which several kinases are activated sequentially by phosphorylation
How does the elevation of cyclic AMP in eukaryotic cells lead to altered transcription of certain genes?
- cAMP binding to protein kinase A causes dissociation of catalytic from regulatory subunits, exposing nuclear localization sequences on catalytic subunits.
- these can translocate onto the nucleus where they can phosphorylate and activate cAMP-regulated gene regulatory proteins (CREBs), which control genes containing cAMP-sensitive regulatory elements (CREs).
How do excitatory and inhibitor neurotransmitters differ in their effects on ligand-gated ion channels?
- Excitatory neurotransmitters (acetylcholine, glutamate) bind to cation-selective receptors and allow ions like Na+ to enter, depolarizing the membrane
- Inhibitory neurotransmitters (GABA, glycine) bind to anion-selective receptors and allow anions like Cl to enter, hyperpolarizing the membrane.
What mechanisms contribute to termination of GPCR-mediated signal transduction?
- Acceleration of GTPase activity by RGS proteins
- Phosphorylation of the GPCR by GRK
- Breakdown of cAMP by PDE
- β-Arrestin binding to the GPCR
cAMP is a second messenger that _________
leads to phosphorylation of cytoplasmic and nuclear proteins by PKA
List 4 characteristics of cytokine receptors:
- can have long disordered regions ranging over 600 residues
- can bind more than one kind of cytokine, even as many as ten different cytokines
- diverse number of extracellular domains
- transmembrane proteins with extracellular, intracellular and transmembrane regions
Cytokine are proteins that….
have diverse function, including one protein that can be either anti-inflammatory or pro-inflammatory.
If the common gamma chain acquired a mutation that inhibited PI3K/Akt signaling, the cell would be more likely to ____ .
undergo apoptosis
In Gq signaling, cytoplasmic calcium levels increase as a result of ……
passive diffusion of calcium from the ER through gated channels
Gleevec (imatinib) treatment produces a prolonged remission (but not a cure) of most cases of CML. In all the responsive cases, the Abl tyrosine protein kinase activity in the cancer cells has been activated by…….
aberrant recombination that caused loss of the inhibitory domain from the catalytic domain
Which enzymes phosphorylate licensing factors to initiate replication?
CDK2
DDK
Cell surface receptors with seven transmembrane domains signal by….
acting as a guanine nucleotide exchange factor
Inositol tri-phosphate, IP3, is produced by which enzyme activity?
phospholipase C
List characteristics of replication
- owes its accuracy to 3’ and 5’ exonucleolytic activity of DNA polymerases or associated proteins. This can remove a mismatched terminal nucleotide (proofreading)
- involves Okazaki fragments because synthesis occurs only in the 5’ to 3’ direction
- begins with the formation of an RNA primer
- requires proteins like primase, ligase, helicase, and others
In eukaryotic DNA replication….
Topoisomerases catalyze changes in the linking number, facilitating untwisting of the parental DNA strands. Since changing the linking number is a transesterification, it protects the integrity of the DNA and occurs without the need of additional energy.
How many initiation sites are there in eukaryotic DNA replication?
multiple
In eukaryotic replication, helicases open the replication fork. How is this powered?
requires the hydrolysis of ATP
In eukaryotic DNA replication, which strand requires the formation of Okazaki fragments?
The lagging strand requires the formation of Okazaki fragments because it has the 5’-end oriented toward the fork
What is the role of ligase in DNA replication?
Ligase simply forms the phosphodiester bond between adjacent nucleotides after the gap has been filled.
What is the function of the RNA component of telomerase?
The RNA component acts as a template for the synthesis of a segment of DNA.
Where are telomeres located?
Telomeres are at the 3’-end of each strand so that the 5’-ends can be replicated
Telomerase is a reverse transcriptase that recognizes…
a G-rich single strand of DNA
Define transition mutation
- mutation that results from substitution of one purine for another or of one pyrimidine for another
- point mutations
Define transversion
occurs when a purine is substituted for a pyrimidine or vice versa
Define frame shift
results from the insertion of one or two bases into the DNA chain
What mutation is frequently caused by chemicals (like acridine) that intercalate into DNA?
frame shift mutation
A missense mutation…
codes for a different amino acid
A nonsense mutation…
is when the code was changed to a stop signal
Homologous recombination involves….
a four-stranded intermediate (Holliday junction) which can be cut in either of two ways
What are the functions of chaperones?
- assist the covalent folding or unfolding of proteins
- prevent formation of aggregates
- responsive to cell stress
- assist in protein degradation by leading proteins to protease systems
What are most chaperones?
heat shock proteins
Disorders associated with mutations in
chaperones can affect….
muscle, bone, and/or the central nervous system
List 4 examples of PTM functions:
recognition signal, protein degradation, histone/DNA modifications, activity regulation
What is the function of proteolytic processing and conformational change?
activation
What is the function of PTM-dependent proteolysis?
Degredation
What are the functions of PTM-dependent recognition?
activation, interaction, localization and secretion
What are the functions of reversible multi-site PTMs?
dynamic regulation or modulation of protein activity and protein-protein and protein-DNA interactions
What diseases do large aggregates cause?
Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis
How is protein degradation a part of protein homeostasis?
- controls certain cellular processes
- getting rid of, and recycling garbage (misfolds, damaged proteins, large aggregates)
ubiquitin-proteasome proteolysis
for proteins that are targeted for degradation as part of cellular regulation
Lysosomal digestion
membrane-bound organelles containing proteases that can degrade exogenous proteins or aged/damaged organelles
