Receptors & Cell Signaling Flashcards
________ is the basis for maintaining homeostasis, cell growth, division and differentiation
Cell signaling
What generic types of disease occur with errors in cellular signaling?
Cancer, diabetes, autoimmunity
What hormone is produced by fat cells to tell the hypothalamus the body is satiated?
Leptin
1) A ________ causes a signaling cell to synthesize and secrete a ________ molecule
Stimulus ; signaling
2) The signal is transported to a __________, where it binds to a _____________ or infiltrates the membrane and binds to an ______________ (aka signal transduction)
Target cell ; receptor protein ; intracellular receptor
3) Signaling molecule-receptor complex _______ or ________ intracellular signaling proteins in the cell
Activates ; inhibits
4) __________ alter the activity of different components downstream and generate _______________
Effectors ; secondary messengers
Type of signal that is transported via blood (think hormone)
Endocrine
Epinephrine released by the adrenal medulla that acts on the heart muscle is an example of what type of signaling? (Think long-distance and long lasting - hours to days, freely diffusing signals)
Endocrine
Type of signal that diffuses to a neighboring target cell of a different cell type
Paracrine
What type of signal is at work when Leydig cells synthesize and secrete testosterone, which induces spermatogensis by acting on Sertoli and germ cells? (Think local signaling, short-lied signals)
Paracrine factor
Neurotransmitters are often what type of signal?
A) Autocrine
B) Paracrine
C) Endocrine
D) Direct/Juxtacrine
B) Paracrine
Short-lived and close to target receptors
Type of signal where secreting cells express surface receptors for the signal they produce
Autocrine
Growth factors in cancer cells often involve what type of cell signaling?
Autocrine
__________ signaling is common in chemokines: interleukin-1 produced by T-lymphocytes promote their own replication in immune response
Autocrine
This type of signal binds to a signaling cell which then binds to a receptor on the target cell
Direct/Juxtacrine
Which signals can can freely diffuse across the membrane?
A) large, uncharged, polar
B) Ions
C) Hydrophobic
C) Hydrophobic
Large, uncharged, polar signals require an active transport mechanism.
Ions: Ion channels
Small, uncharged, polar: gradient-dependent diffusion
Lipophilic signals interact with receptors on the ________ of the cell and must be bound to _________ to be transported through the bloodstream. Lipophilic signals have ______ half lives.
inside ; carrier proteins ; long (hours to days)
The two types of lipophilic receptors are:
Cytoplasmic receptors and Nuclear Receptors
Cytoplasmic receptors
Form complexes w/ HSP. Dissociates from HSP upon signal binding and translocates to the nucleus and binds to a DNA sequence, altering the rate of transcription
Nuclear receptors
Present in nucleus bound to DNA. Alters transcription of certain genes after signal binding.
Signals that are water-soluble and cannot diffuse through cellular and nuclear membranes are _________ signals.
Hydrophilic
Hydrophilic signals bind to __________, trigger activation of events ___________. They are generally small and derived from __________. Hydrophilic signals have ________ half-lives.
Surface receptors ; downstream ; amino acids ; short (seconds to minutes)
What are the two types of hydrophobic receptors?
G protein-coupled receptors (GPCR)
Receptor tyrosine kinases
GPCR involves:
Signaling mediated by ___________, effector proteins, second _________, and ___ (#) alpha helices
G proteins ; messengers ; 7
Receptor Tyrosine Kinases are mediated by ________ G proteins and ____________
RTKs contain ___ alpha-helical transmembrane domain.
Monomeric ; protein kinases ; 1
Lipophilic vs. hydrophilic medications
oral contraceptives contain ________ signaling molecules that have long half-lives (hours to days) and are hence, taken ________
Lipophilic ; daily
Lipophilic vs. hydrophilic medications
________ signaling molecules had short half-lives (seconds to minutes) and are administered at the time they are needed. For example: epinephrine is used to combat acute allergic rxns
Hydrophilic
Graves’ disease and other thyroid disease result in a(n) ________ in TSH and a(n) _________ in T3 and T4.
Decrease ; increase
Graves’ disease : list symptoms and treatment options
Most common amongst women, presents by 40s
Present with weight loss, tachycardia, insomnia, pretibial myxedema, ophtalmopathy (exophthalmos), thyroid goiter
Treatment: surgical resection of the thyroid gland, radioactive iodine, pharmacological intervention
GPCRs have an _____-cellular domain that binds to a signal, a _________ domain composed of ___ helices, and an _____cellular domain that interacts with trimeric _________.
Extra- ; trans- ; 7 ; intra ; G proteins
GPCRS are arranged in a _________ pathway within the membranes. They include an extra cellular _______ bond. Have a C-terminus tethered to the ______.
Circular ; disulfide ; membrane
Binding epinephrine to B-adrenergic repceptor causes __________ in bronchial and intestinal smooth muscles
BUT causes ________ in the heart.
Binding produces the same secondary messenger ________ in both tissues but the downstream signaling pathways diverge resulting in different physiological pathways.
Relaxation ; contraction ; cAMP
Epinephrine can be administered to relieve bronchospasms during an asthma attack or to restore cardiac rhythms after arrest. Side effect of albuterol - can cause tachycardia.
Trimeric G proteins contain ____ distinct subunits with _____ase activity. They act as a molecular _________.
3 (alpha, beta, gamma) ; GTPase ; on-off switch
T or F:
Trimeric G proteins are active when alpha subunit is bound to GDP.
False. Trimeric G proteins are active when alpha subunit is bound to GTP and inactive when bound to GDP.
GEF (guanine nucleotide exchange factors) are proteins that ________ G-proteins by promoting exchange of GDP for GTP.
Activate
GAP (GTPase-activating proteins) _______ G proteins by promoting GTPase activity
Inactivate, or speed up the inactivation of G proteins as GTPase activity hydrolyzes GTP to GDP and Phosphate (Pi)
A(n) ___________ is typically a embrace-bound enzyme that catalyze rxns that produce _________ messengers.
Effector protein ; second
CAMP,cGMP, DAG, IP3 and Ca2+ are all examples of _________
Secondary messengers
Slide 27-30
Finish
Gs activation ________ adenylate Cyclase
Activates
Adenylyl Cyclades generates _______ from ATP, which activates ____
cAMP ; PKA
PKA directly regulates many pathways via phosphorylation
Gi activation _______ adenylate cyclase
Inhibits
With Gi, cAMP is not produced and PKA is not activated
Gt activation by _______ activates cGMP PDE
Light
cGMP PDE catalyze the hydrolysis of cGMP to 5’-GMP
Lower concentration of cGMP causes hyperpolarization of visual cells
Gq activation by phospholipase C ________ PLC
Activates
PLC cleaves PIP2 into _____ and ______, which translocates to ER and opens ligand-gated ______ channels, increasing _____ concentration, which causes translocation of PKC to plasma membrane where it is activated by DAG.
DAG ; IP3 ; Ca2+
T or F
Activators of cGMP PDE increases concentration of cellular cGMP, leading to smooth muscle relaxation and vasodilation (think Viagra, levitate, cialis).
False. Inhibitors of cFMP PDE increases concentration of cellular cGMP that leads to smooth uncle relaxation and vasodilation.
Patients may take nitrates (NO) to ______ blood pressure.
Should patients on nitrates take drugs like cialis or viagra?
Lower ; NO - the combo can lead to extreme vasodilation and fatal drops in blood pressure
Albuterol is a ________ and _____-Philip molecule that binds to and activate __________ receptors
B-against ; hydro- ; b-andrenergic
Used to treat asthma, bronchitis, COPD. Unresponsive pts can be given epinephrine.
Histamines (derived from histidine) bind to 4-histidine in ________. So antihistamines block histamine binding to _________ which prevents the allergic response.
GPCR ; GPCR
Common antihistamines: cetirizine (zyrtec), loratadine (Claritin), diphenhydramine (Benadryl)
Cholera toxin prevents the _______ of Gsa and pertussis toxin prevents the ________ of Gia
Inactivation ; activation
