Receptors & Cell Signaling Flashcards
This type of signal (hormone) is transported via blood. It is long-distance signaling, long-lasting, and freely diffusing.
Endocrine
What is an example of endocrine signaling?
Epinephrine
***Epinephrine released by adrenal medulla and acts on heart muscle
This type of signal diffuses to neighboring target cell of a different cell type. It is local signaling with a short-lived signal.
Paracrine
What is an example of paracrine signaling?
Testosterone
***Leydig cells synthesize and secrete testosterone which induces spermatogenesis by acting on Sertoli and germ cells
This type of signal occurs when secreting cells express surface receptors for the signal or release to cells of the same type.
Autocrine
What is an example of autocrine signaling?
IL-1 produced by T-lymphocytes promote their own replication during an immune response. Also the action of growth factors in cancer cells.
This type of signal binds to signaling cell which then binds to receptor on the target cell.
Direct/Juxtacrine
What is an example of direct/juxtracrine signaling?
Heparin-binding epidermal growth factor (HB-EGF) binds to EGF receptor. Also in immune cells.
T/F. Signaling molecules can only occur in one type of signaling, depending on what the signal is.
False. Some signaling molecules participate in more than one type of signaling.
Signals can either be _____-soluble or _____-soluble.
Water (hydrophilic)
Lipid (hydrophobic)
(HYDROPHOBIC/HYDROPHILIC) signaling cannot penetrate the plasma membrane. It interacts with specific receptors at the cell surface.
Hydrophilic
What are examples of hydrophilic signals?
Epinephrine, insulin, glucagon, etc.
In hydrophilic signaling, the signal-molecule receptor complex initiates production of _______ _______ molecules inside the cell. These are generally small and derived from AA, polypeptides, or through lipid metabolism. Have shorter half-lives and trigger a downstream cellular response.
Second messenger
What kind of receptors are involved in hydrophilic signaling?
GPCRs
RTKs
(HYDROPHOBIC/HYDROPHILIC) signals pass through plasma membrane of target cell. The signal binds to specific receptor proteins inside the cell.
Hydrophobic (also called Lipophilic)
In lipophilic signaling, the signaling molecule-receptor complex acts as a _______ _______. Receptors are located in cytosol or nucleus. Have long half-lives.
Transcription factors
***Several families of DNA binding transcription factors. Both cytoplasmic and nuclear receptors regulate the transcription of specific genes.
In lipophilic signaling, cytoplasmic receptors exist in an inactive form complexed with _______. Upon binding to ligand, ______ dissociates. The hormone-receptor complex translocates to the nucleus where it binds to a specific DNA sequence called the _______ in the promoter region of specific genes.
HSP90
HSP90
HRE (hormone response element)
In lipophilic signaling, nuclear receptors are already present in ________ bound to DNA. The hormone allows for interactions with additional proteins and activate the complex.
Nucleus
What are some examples of lipophilic signaling?
Steroid hormones
Thyroid hormones
Retinoids
What is the structural motif of GPCRs?
Extracellular domain – binds to signal
Transmembrane domain – composed of 7 alpha-helices
Intracellular domain – interacts with G proteins
In GPCR signaling, the ligand binds to the ECD and causes a conformation change in the GPCR. ICD activates its G-protein by triggering the exchange of ______ for ______ (acts as a GEF). The activated G-protein then interacts with membrane-bound effector protein which will produce a second messenger.
GDP
GTP
Put the following steps in order from first to last:
A. 2nd messenger B. Biological response C. GPCR D. Effector enzyme E. Trimeric G-protein F. Targets of 2nd messenger
1) C. GPCR
2) E. Trimeric G-protein
3) D. Effector enzyme
4) A. 2nd messenger
5) F. Targets of 2nd messenger
6) B. Biological response
Trimeric G-proteins contain three subunits, which are…
Alpha
Beta
Gamma
An inactive G-protein has ______ bound to its ______ subunit. To become active, the G-protein must exchange its ______ for ______.
GDP
Alpha
GDP
GTP
The active, GTP-bound alpha subunit (of GPCR complex) separates from beta and gamma subunits. To return to its inactive state, the intrinsic _______ activity of the G-protien hydrolyzes its bound GTP to GDP and phosphate. This action is accelerated by a ______.
GTPase
GAP
***Remember a GEF exchanges GDP for GTP, GAP hydrolyzes GTP back to GDP and phosphate.
Signal desensitization is the ability to “turn off” a signal. What are the different mechanisms of doing so?
Drop in hormone levels
Remove the signaling molecule
Receptor sequestration
Receptor destruction
This type of G-protein stimulates adenylate cyclase (effector protein that activates cAMP).
Gs
This type of G-protein stimulates cGMP phosphodiesterase. The GPCR is stimulated by light.
Gt
***The GPCR is called Rhodopsin (used in eye cells)
This type of G-protein inhibits adenylate cyclase.
Gi
This type of G-protein activates phospholipase C (PLC), which activates PIP2 and causes its division into DAG and IP3. DAG activates PKC, which goes on to phosphorylate target proteins to alter their activities, and induce release of Calcium from ER/SR. IP3 also induces release of calcium, which leads to the Calcium-calmodulin complex. This complex activates certain proteins.
Gq
STUDY table 7.2 (page 103)
Study 5 minutes
Enzymes hydrolyze cyclic nucleotides (i.e., cAMP) to regulate their cellular levels. What hydrolyzes cAMP to AMP?
cAMP phosphodiesterase
cGMP _________ hydrolyzes cGMP to 5’-GMP.
Phosphodiesterase
Inhibitors of cGMP phosphodiesterase increase concentration of cellular cGMP and prolongs its effects for a greater amount of time, leading to smooth muscle relaxation and vasodilation. This results in an _________.
Erection
***i.e., Viagra, Levitra, Cialis
This inhibits the activity of PDE (phosphodiesterase), leading to the accumulation of cAMP, leading to an increased heart rate.
Caffeine
_______ toxin prevents the inactivation of Gs-alpha subunit. There is a covalent modification of alpha subunits of Gs. ADP ribosylation of _____ in Gs alpha decreases the intrinsic GTPase activity (GAP), causing the Gs alpha to remain active (GTP bound form) and continuously stimulate adenylate cyclase, resulting in overproduction of cAMP.
Cholera
Arg
An overabundance of cAMP (from cholera toxin) in intestinal cells opens the _______ channels, resulting in loss of electrolytes and water. This results in diarrhea.
Chloride
The ________ toxin prevents the activation of Gi alpha subunit. ADP ribosylation of ______ on Gi alpha prevents the activation and dissociation of this subunit from the trimeric G-protein. The result is less inhibition of adenylate cyclase and an overproduction of cAMP.
Pertussis
In airway epithelial, pertussis toxin causes loss of fluids and excessive mucous secretion, which presents as…
Whooping cough
Explain the mechanism of water secretion.
- Toxin activates adenylate cyclase to produce cAMP
- cAMP activates the CFTR
- Leads to secretion of chloride
- Builds up negative potential across membrane
- Leads to secretion of Na+
- Results in net secretion of NaCl
- NaCl builds up an osmotic gradient across membrane
- Leads to water secretion
This is produced in epithelial cells from Arginine and is responsible for the relaxation of smooth muscles.
NO (nitric oxide)
NO diffuses to neighboring muscle and activates _______ _______, leading to the production of _______. This results in smooth muscle relaxation and vasodilation.
Guanylate cyclase
cGMP
__________ and other nitrates (the medicines taken by patients with angina) decompose to form NO and help to lower blood pressure.
Nitroglycerine
Patients that take nitrates should NOT take drugs that inhibit ________ (i.e., Viagra) as the combination can lead to extreme vasodilation (erection won’t go away) and fatal drops in blood pressure.
cGMP phosphodiesterase
_________ are used to treat allergies. The symptoms of an allergy (sneezing, runny nose, and itchy eyes) are caused by _________.
Antihistamines
Histamine
Histamine is generated from the amino acid ________, and is a ligand that binds to four histamine GPCRs (H1 thru H4).
Histidine
Antihistamines are lipophilic compounds that block the effects of histamine to the _____ GPCR. Examples are Zyrtec, Claritin, Diphenhydramine, Benadryl, etc.
H1
What is the structural motif of RTKs?
ECD = contains signaling molecule binding site Transmembrane = Single helix that spans it ICD = Tyrosine kinase activity
Put the following steps of RTK signaling in order:
A. Tyrosine phosphorylated (autophosphorylation)
B. RTK signaling terminated
C. Signal binds to ECD
D. Phosphotyrosine recognized- SH2 domain of Grb2 binds
E. RAS signals downstream to MAPK pathway (Raf)
F. Grb2 activates SOS (acts as GEF for Ras)
G. Raf activates Mek
H. Mek activates Erk
I. Erk phosphorylates target proteins
J. Alteration in gene transcription and protein activity
K. Conformation change that causes receptor dimerization
1) C.
2) K.
3) A.
4) D.
5) F.
6) E.
7) G.
8) H.
9) I.
10) J.
11) B.
RTKs are often associated with cancers because they can mutate into _________.
Oncogenes
Small G proteins like _____ superfamily are different from heterotrimeric G proteins. Play an important role in transaction of signals from membrane receptors to effector proteins (kinases). They monomeric G proteins that have a single polypeptide chain and intrinsic GTPase activity (GAP). Mutations that affect the GAP activity can lead to cancer.
RAS
RTKs are the target of pharmacological inhibitors because excessive signaling from mutated or over expressed RTKs is associated with cancer. For example, the breast cancer drug _______ targets _______, which belongs to the family of EGF-binding RTKs.
Herceptin
HER2
Mutant forms of RAS, or its GEFs or GAPs have been implicated in a wide range of human cancers. 30-50 percent of lung and colon and 90 percent of pancreatic cancers are associated with activation point mutations in RAS. Mutations decrease _______ activity and lock it in active, GTP-bound state.
GTPase (GAP)
This is a condition marked by growth of tumors in nerve tissue. It is caused by inactivating mutation in neurofibromin (NF-1) gene, which encodes a GAP for RAS. RAS has uncontrollably activated pathways for nerve tissue growth. Leads to optical glioma, macrocephaly, learning disabilities.
Neurofibromatosis
