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Hormones, Cytokines, Interleukins, Growth Factors & metabolites are examples of what molecules?
Signaling molecules
True or False? Excessive, deficient or inappropriate production of hormones and other regulatory signaling molecules are major causes of diseases.
True
Hormones are synthesized by ___ ___ glands.
DUCTLESS ENDOCRINE glands
____ signaling acts on cells that synthesize them. (Auto or Para)
Autocrine
____ signaling acts on NEARBY cells of the same type. (Auto or Para)
Paracrine
Cytokines: Immune System ; Hormones: _____
Endocrine system
What are the 2 modes of intercellular signal transduction?
Contact dependent or Juxtacrine
Contact independent
What mechanisms does juxtacrine transduction use to communicate?
Via
1) Gap Junction
2) Surface protein + Receptor protein
(___) allows direct transfer of small ions, metabolites, and second messenger molecules between 2 neighboring cells.
Gap junctions
(___) signaling is when a cell secretes molecules into its immediate environment resulting in a localized action.
Paracrine
(___) signaling is when hormones from the center cell are brought directly through the bloodstream to their distant target.
Endocrine
(__) are proteins containing a binding site specific for a single chemical messenger and another binding site involved in transmitting the message
Receptors
Classification of Hormones.
What is the solubility property of Class 1 Hormones?
Lipophilic
Classification of Hormones.
What is the solubility property of Class 2 Hormones?
Hydrophilic
Classification of Hormones.
Where can the receptors of Class 1 Hormones be found?
Intracellular
Classification of Hormones.
Where can the receptors of Class 2 Hormones be found?
Extracellular
Which class of hormones require Secondary Messengers?
Class 2
What are 2 examples of Amino-acid derived hormones?
Thyroid Hormones
Catecholamines (produced by adrenal medulla) e.g. Epinephrine & Norepinephrine
What is the precursor or amino-acid derived hormones?
Tyrosine
What is the parent compound of Steroids?
Cholesterol
Give examples of MAIN Steroids.
Glucocorticoids
Mineralocorticoids
Sex Hormones
Hormones produced by the placenta
Hormontes produced by Kidney/Liver
Based on chemical composition, what are the three main classifications of hormones?
Amino Acids
Polypeptides
Steroids
What solubility property characterizes Class I hormones?
Lipophilic/Hydrophobic.
Where are the receptors for Class I hormones typically located?
Intracellular (Cytoplasm, Nucleus).
What solubility property characterizes Class II hormones?
Hydrophilic/Lipophobic.
Where are the receptors for Class II hormones typically located?
Extracellular (Cell surface/Plasma Membrane).
For Class I hormones, what acts as the intracellular messenger or signal?
The Hormone-receptor complex.
For Class II hormones, what is the role of the hormone itself in terms of intracellular signaling?
The hormone acts as the 1st messenger.
Name at least three common second messengers involved in Class II hormone signaling.
cAMP
cGMP
PIP3
Ca2+
Kinase-phosphate cascade
If a hormone is derived from cholesterol (a steroid), would its receptor likely be intracellular or extracellular?
Intracellular (because steroids are Class I: Lipophilic).
A hormone that uses cAMP as a second messenger would fall under which classification (Class I or Class II) and have what solubility property?
Class II; Hydrophilic/Lipophobic.
Catecholamines such as Epinephrine and norepinephrin is produced by which organ?
Adrenal medulla
Mineralcocortidcoids such as aldosterone are produced by which organ?
Adrenal cortex
Somatostatin and ADH is produced by which organ?
Hypothalamus
TSH, FSH, LH, GH and ACTH are produced by which organ?
Pituitary gland
Which organ produces Calcitronin
Thyroid
Which of the following is a key role of second messengers in the signal transduction pathway?
To amplify the initial signal received by a single cell surface receptor.
To physically transport the first messenger across the plasma membrane.
To terminate the signal by directly degrading the first messenger.
To bind directly to DNA and alter gene expression without any intermediaries.
To amplify the initial signal received by a single cell surface receptor.
A single first messenger can lead to the production of many second messenger molecules, thereby greatly amplifying the signal's strength.
Which enzyme is responsible for the production of cyclic AMP (cAMP) from ATP?
Phospholipase C
protein kinase A
adenylyl cyclase
Guanyl cyclase
Adenylyl cyclase is the enzyme that catalyzes the conversion of ATP into cyclic AMP (cAMP).
The second messengers IP3 and DAG are both produced from the cleavage of which membrane lipid?
A.Cholesterol
B.Phosphatidylinositol 4,5-bisphosphate (PIP2)
C.Phosphatidylcholine
D.Sphingomyelin
B.Phosphatidylinositol 4,5-bisphosphate (PIP2)
Which second messenger primarily acts by causing the release of Ca2+ from intracellular stores, such as the endoplasmic reticulum?
A.Cyclic AMP (cAMP)
B.Diacylglycerol (DAG)
C.Inositol Trisphosphate (IP3)
Inositol Trisphosphate (IP3)
Calcium ions (Ca2+) serve as a versatile second messenger. One common way Ca2+ mediates cellular responses is by binding to which protein, leading to the activation of other enzymes?
A.Tubulin
B.Actin
C.Calmodulin
D.Myosin
Calmodulin
Which of the following second messengers is a gas and can diffuse across cell membranes to act on neighboring cells?
A.
Diacylglycerol (DAG)
B.
Inositol Trisphosphate (IP3)
C.
Nitric Oxide (NO)
C. Nitric oxide
What is a characteristic feature of how second messenger levels are regulated within the cell?
A.
They remain at consistently high concentrations at all times.
B.
They are only produced once per cell's lifetime.
C.
They are typically produced slowly over several hours to ensure prolonged signaling.
D.
Their levels are exquisitely controlled temporally and spatially by rapid production and removal/degradation.
D.
Their levels are exquisitely controlled temporally and spatially by rapid production and removal/degradation.
Protein Kinase A (PKA) is primarily activated by which of the following second messengers?
A.
Diacylglycerol (DAG)
B.
Calcium ions (Ca2+)
C.
Inositol Trisphosphate (IP3)
D.
Cyclic AMP (cAMP)
D.
Cyclic AMP (cAMP)
Which type of receptor directly forms an ion channel upon ligand binding?
ionotropic receptor
When a ligand binds to a metabotropic receptor, what is always activated?
An ion channel directly opens on the receptor.
A G-protein.
A G-protein.
Which type of receptor primarily causes a rapid change in membrane potential due to immediate ion flow?
Ionotropic receptor
Metabotropic receptor
Ionotropic receptor
A Class II hormone, which cannot rapidly cross the plasma membrane, would typically bind to which type of receptor?
Intracellular receptor
Ionotropic receptor
Ionotropic receptor
Which receptor type's activation can lead to the production of secondary messengers?
Metabotropic receptor
ionotropic receptor
Metabotropic receptor
True or False: Nicotinic receptors can be found in both the Sympathetic Nervous System (SNS) and Parasympathetic Nervous System (PNS), while muscarinic receptors are exclusively found in the PNS.
Answer: True
What is the direct consequence of a chemical messenger binding to an Ion Channel Receptor?
A.The receptor immediately detaches from the plasma membrane.
B.The channel undergoes a conformational change, allowing specific particles to pass through.
C.It initiates a cascade of second messenger production.
D.The receptor synthesizes a new protein.
B.The channel undergoes a conformational change, allowing specific particles to pass through.
Which of the following ions are explicitly mentioned as being able to travel through ligand-gated ion channels?
A.Sugars and amino acids
B.K+, Na+, Cl− and Ca2+
C.Fe2+ and Zn2+
D.Large protein molecules
K+, Na+, Cl− and Ca2+
The Nicotinic acetylcholine receptor is provided as an example of which type of plasma membrane receptor?
A.Serine/Threonine Kinase Receptor.
B.receptor linked to a G-protein.
C.Ion Channel Receptor.
D.receptor that binds kinases
An Ion Channel Receptor.
Which specific messenger binds to Tyrosine Kinase Receptors?
steroid hormone.
neurotransmitter
growth factor
cytokine dimer
Growth factor
What type of messenger is listed for Serine/Threonine Kinase Receptors?
cytokine dimer.
lipid
amino acid
ion
cytokine dimer
What is a common feature of receptors that are kinases or bind kinases, regarding their intracellular domain?
A. The intracellular domain is a kinase that is activated when the messenger binds to the extracellular domain.
B.The intracellular domain forms an ion channel for calcium influx.
C.The intracellular domain directly binds to DNA to initiate transcription.
D.The intracellular domain is a storage site for second messengers.
A. The intracellular domain is a kinase that is activated when the messenger binds to the extracellular domain.
What type of phosphorylation process is characteristic of receptors that are kinases or bind kinases?
Autophosphorylation
Glycosylation
Ubiquitination
Dephosphorylation
Autophosphorylation
If a receptor's intracellular domain is described as being a 'kinase' that phosphorylates an amino acid residue on itself, to which major class of plasma membrane receptors does it belong?
A.G-Protein Coupled Receptors
B.Receptors that are Kinases or Bind Kinases
C.Nuclear Receptors
D.Ion Channel Receptors / Ligand-Gated Ion Channels
B
2. What type of chemical messenger commonly binds to Tyrosine Kinase Receptors?
A.
Calcium ions (Ca2+)
B.
Neurotransmitters like acetylcholine
C.
Steroid hormones
D.
Growth factors or insulin
Growth factors or insulin
What is 'dimerization' in the context of TKR activation?
A.
The breakdown of the receptor into two smaller molecules.
B.
The addition reaction where two molecules of the same compound react with each other.
C.
The removal of phosphate groups from the receptor.
D.
The transport of the receptor from the extracellular to the intracellular space.
The addition reaction where two molecules of the same compound react with each other.
Immediately after dimerization of the TKR, what is the next step in the signal transduction pathway?
A.
The intracellular tyrosine kinase domains phosphorylate each other.
B.
The phosphotyrosine residues form specific binding sites.
C.
Ras protein exchanges GDP for GTP.
D.
The receptor is internalized into the cell.
The intracellular tyrosine kinase domains phosphorylate each other.
What is the purpose of the phosphotyrosine residues formed after autophosphorylation?
A.
They directly activate gene transcription.
B.
They become specific binding sites for signal transducer proteins like the SH2 domain.
C.
They serve as a new binding site for the original growth factor.
D.
They release second messengers into the cytoplasm.
They become specific binding sites for signal transducer proteins like the SH2 domain.
Which protein is described as a GEF (guanine nucleotide exchange factor) that activates Ras protein by exchanging GDP for GTP?
A.
SOS (Son of Sevenless)
B.
Grb2
C.
MAP kinase
D.
Raf
SOS (Son of Sevenless)
SOS is a GEF (guanine nucleotide exchange factor) which activates the exchange of GTP for GDP on the Ras protein'.
. What is the immediate protein activated by Ras (once Ras has GTP bound)?
A.
Grb2
B.
Raf
C.
A gene transcription factor
D.
SOS
Raf
he MAP kinase cascade ultimately terminates at what type of molecule?
A.
A secondary messenger
B.
An ion channel
C.
A gene transcription factor
The MAP kinase cascade terminates at a gene transcription factor, thereby regulating transcription of certain genes'.
Mutation of certain TKR genes can result in the expression of receptors that assume an activated conformation even in the absence of a growth factor. What is a potential consequence of this type of mutation?
A.
Increased production of cyclic AMP (cAMP) as a primary response.
B.
Formation of mutated chains that can act as oncogenes and contribute to cancer.
C.
Reduced sensitivity to other growth factors in the extracellular environment.
D.
Decreased cell survival and proliferation, leading to cell death.
Formation of mutated chains that can act as oncogenes and contribute to cancer.
Which of the following is NOT listed as utilizing Tyrosine Kinase Receptors?
A.
Acetylcholine
B.
Platelet derived growth factor
C.
Insulin
D.
Epidermal growth factor
Acetylcholine
What distinguishes the Insulin Receptor's initial structure from other Tyrosine Kinase Receptors (TKRs) like those for growth factors?
A.It does not have intrinsic kinase activity.
B.It is an intracellular receptor.
C.It exists as a preformed dimer in the membrane.
D.It is a monomer that dimerizes upon ligand binding.
C.It exists as a preformed dimer in the membrane.
Which subunits of the Insulin Receptor undergo autophosphorylation upon insulin binding?
A.
The β subunits.
B.
Both α and β subunits.
C.
Only the insulin molecule itself.
D.
The α subunits.
A.
The β subunits.
What is the role of Insulin Receptor Substrate (IRS) in insulin signaling?
A.
It directly activates Ras protein without prior phosphorylation.
B.
It acts as a primary binding site for insulin itself.
C.
It directly transports glucose into the cell.
D.
It is phosphorylated by the activated receptor, creating multiple binding sites for proteins with SH2 domains.
It is phosphorylated by the activated receptor, creating multiple binding sites for proteins with SH2 domains.
Which protein directly binds to a site on IRS and leads to the activation of the Ras protein and the MAP kinase pathway?
Grb2
Phospholipase Cy
Protein Kinase B
Grb2
The Grb2 → Ras → MAP kinase pathway, activated by the Insulin Receptor, primarily mediates which cellular effects?
A.
Cell growth, proliferation, or differentiation.
B.
Lipogenesis and lipolysis.
C.
Glucose transport and synthesis.
D.
Immediate release of Ca2+ from intracellular stores.
A. Cell growth, proliferation, or differentiation.
Which enzyme binds to a site on IRS and leads to the activation of Protein Kinase B (PKB)?
A.PI3-kinase
B.Adenylyl cyclase
C.Raf
D.Phospholipase Cy
A.PI3-kinase
Protein Kinase B (PKB) is described as a serine/threonine kinase that mediates many metabolic effects of insulin. Which of the following is NOT listed as one of these effects?
A.
Synthesis of new receptors.
B.
Glucose transport.
C.
Gluconeogenesis.
D.
Lipogenesis.
A.
Synthesis of new receptors.
The ability of the activated Insulin Receptor to lead to distinct downstream signaling pathways (e.g., Grb2-Ras-MAP kinase and PI3-kinase) is an example of what concept in signal transduction?
A.
Convergence.
B.
Feedback inhibition.
C.
Amplification.
D.
Divergence.
D.
Divergence.
Besides the Grb2-Ras-MAP kinase and PI3-kinase pathways, which other signal transduction intermediate is mentioned as being able to directly dock with the insulin receptor?
A.
Phospholipase C$\gamma$
B.
Ras protein
C.
G-protein
D.
cAMP
Phospholipase Cy
What kind of receptor is the Insulin Receptor a member of?
A.
Tyrosine kinase family
B.
Steroid hormone receptor
C.
Ligand-gated ion channel receptor
D.
G-protein coupled receptor
Tyrosine kinase family
Does the JAK-STAT receptor itself possess intrinsic kinase activity?
No, it associates with a separate tyrosine kinase.
Yes, it has intrinsic tyrosine kinase activity.
No, it associates with a separate tyrosine kinase.
The receptor itself has no intrinsic kinase activity but binds or associates itself with the tyrosine kinase JAK or the Janus kinase.
What are the three main components of the JAK-STAT system?
A.
Ligand, Second Messenger, and Kinase.
B.
Receptor, G-protein, and Adenylyl cyclase.
C.
Receptor, Janus kinase (JAK), and STAT protein.
D.
Tyrosine kinase, Serine/Threonine kinase, and Receptor.
C.
Receptor, Janus kinase (JAK), and STAT protein.
What happens immediately after a ligand (e.g., cytokine) binds to the JAK-STAT receptor?
A.
The receptor forms a dimer with another identical receptor.
B.
JAK adds phosphate to the receptor.
C.
STAT protein directly binds to the ligand.
D.
The receptor enters the nucleus directly.
B.
JAK adds phosphate to the receptor.
What is the role of the Janus kinase (JAK) in the JAK-STAT pathway?
A.
It transports the ligand into the cell.
B.
It acts as a second messenger within the cytoplasm.
C.
It binds directly to DNA to initiate transcription.
D.
It adds phosphate groups to the receptor and then to STAT proteins.
It adds phosphate groups to the receptor and then to STAT proteins.
After STAT proteins bind to the phosphorylated receptor, what happens to them?
A.
They are immediately degraded by proteasomes.
B.
They release their bound phosphate groups.
C.
They activate G-proteins.
D.
They are phosphorylated by JAKs to form a dimer.
STAT protein then binds to the phosphate and STATs are phosphorylated by JAKs to form a dimer'.
What is the final destination of the STAT dimer after it is formed?
A.
The plasma membrane.
B.
The nucleus.
C.
The endoplasmic reticulum.
D.
The extracellular matrix.
The nucleus.
What is the ultimate cellular effect caused by the STAT dimer binding to DNA?
A.
Activation of second messengers like cAMP.
B.
Transcription of target chains.
C.
Ion channel opening.
D.
Hydrolysis of ATP.
Transcription of target chains.
What type of chemical messenger typically binds to JAK-STAT Receptors?
A.
Insulin
B.
Growth factor
C.
Steroid hormone
D.
Cytokine
Cytokine
The JAK-STAT system is described as having a 'more direct route for propagation of signal to the nucleus' compared to other tyrosine kinase pathways. What feature primarily enables this directness?
The STAT dimer directly entering the nucleus and binding DNA.
The use of multiple second messengers.
The receptor itself entering the nucleus.
The immediate activation of G-proteins.
The STAT dimer directly entering the nucleus and binding DNA.
What is the general term for enzymes that add phosphate groups, as exemplified by JAK?
A.Nucleases
B.Ligases
C.Kinases
D.Phosphatases
The enzyme that adds phosphate groups are called protein kinases
Proteins in the transforming growth factors superfamily use receptors that have the _____ kinase activity and are associated with SMAD family
serine/threonine