Biochemistry - Signal Transduction Flashcards
1
Q
An important second messenger that internalizes the message carried by intercellular messengers such as peptide hormones and NO by synthesizing cGMP from GTP. It can also function as an autocrine signal.
A
guanylyl cyclase
1
Q
can lower cytoplasmic calcium levels by pumping calcium back into the ER (primary active transport)
A
Ca2+-ATPase
1
Q
Ga-i
A
inhibits the enzyme adenylate cyclase
2
Q
Kinase Targets
A
other kinases, phophotases, metabolic enzymes, transcription factors.
3
Q
Signaling over long distances
A
Endocrine
3
Q
- release of acetylcholine from the nerve terminus of a blood vessel. 2. Acetylcholine binds to receptors on the surface of endothelial cells of the blood vessel wall initiating a signalling cascade that activates an enzyme that converts arginine to target molecule and citrullline. 3. __ diffuses out of endothelial cell and into smooth muscle cell. 4. __ reacts with iron in active site of guanylyl cyclase, stimulating the production of cyclic GMP.5. cGMP initiates a signaling cascade leading to rapid relaxation of smooth muscle cell.
A
Signaling By Nitric Oxide
3
Q
G-protein coupled receptor (GPCR)
A
7 member transmembrane protein receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses.
4
Q
A toxin covalently adds an ADP-ribose to the Ga-i subunit. Inhibited Ga-i cannot inhibit AC, so cAMP levels increase.
A
Pertussis Toxin
5
Q
Hydrophobic signaling molecules
A
bind to carrier proteins outside of the cell but diffuse across plasma membrane to enter cell. Binding of ligand to receptor protein occurs inside cell.
5
Q
Cell-Surface Receptors
A
hydrophilic ligand binds, alteration delivers signal into cell via intracellular proteins.
6
Q
Calmodulin
A
Activated when bound to Ca2+. When activated, wraps around other proteins, changing their conformation.
7
Q
Growth factor binds, causing two monomeric receptors to dimerize. Tyrosine residues on cytoplasm side are trans-autophosphorylated, which alters charge and conformation, creating a new binding site. GRB2 binds at an SH2 domain, recruiting SOS from the cytoplasm to the membrane. SOS binds and stimulates RAS to exchange GDP for GTP, which activates RAS. RAS activates Raf, a kinase that begins a phos-cascade known as MAPK.
A
RTK Signaling
7
Q
Neuronal Signaling Phases
A
- Signaling through the neuron via an electrical potential 2. Signaling to the target cell through the action of a neurotransmitter released at the synapse.
8
Q
covalently adds an ADP-ribose group to an arginine residue og G-alpha subnits.
A
ADP ribosylase
9
Q
A toxin that ADP-ribosylates the Ga-s subunit in the cytoplasm. As a result, Ga-s cannot hydrolyze GTP, leading to constant signaling of AC and production of cAMP.
A
Cholera toxin
10
Q
cGMP
A
Reacts with NO at an iron in its active site to initiate the signal for relaxation in smooth muscle.
11
Q
Signaling over short distances
A
Autocrine + Paracrine
11
Q
Insulin-producing cells of the pancre as are lost. Signal (insulin) never reaches target cells
A
Diabetes, Type I (Autoimmune)
11
Q
G-alpha-1 receptor
A
a2 receptor (inhibits AC)
12
Q
Hormone binds to its receptor in the cytoplasm, causing receptor/ligand complex to translocate to the nucleus, which binds to DNA sequence upstream of ligand-responsive genes, stimulating DNA transcription, thus synthesizing new protein.
A
Steroid Hormone Mechanism
12
Q
Ga-q
A
activates the enzyme phospholipase C
13
Q
Activated alpha subunit separates from the b/g subunits and stimulates Adenylate Cyclase (AC).
A
GCPR Activation, 3rd Step
14
Q
Phosphatase
A
an enzyme that removes a phosphate group from its substrate
14
Q
DAG
A
Formed from PIP cleavage, remains in the membrane.
15
GCPR Activation, 2nd Step
Alpha subunit activated by binding of GTP.
16
Diabetes, Type II (Insulin-Resistant Diabetes)
Insulin is made but target cells become less responsive to ligand binding. Eventually, pancreas synthesis of insulin decreases (B-cell exhaustion).
17
Endocrine
Signaling over long distances
18
IP3
Formed from PIP cleavage, diffuses through cytoplasm where it interacts with ER receptors that open calcium channels, leading to a dramatic increase in cytosolic Ca2+ which binds to PKC, leading it to bind to DAG, activating PKC.
19
Intracellular ligand synthesized from the amino acid arginine. Soluble in both aqueous and lipid media, and readily diffuses through cytoplasm and plasma membranes. Half-life of only a few seconds, can only effect nearby cells.
Nitric oxide
20
A single cell in a mixed population secretes ligands that bind only to its OWN receptor. Or in a group of identical cells, secreted ligands bind receptors on adjacent cells
Autocrine
23
other kinases, phophotases, metabolic enzymes, transcription factors.
Kinase Targets
23
Converts cAMP to the low-energy nucleotide AMP (adenosine monophosphate).
cAMP phosphodiesterase
23
Formed from PIP cleavage, diffuses through cytoplasm where it interacts with ER receptors that open calcium channels, leading to a dramatic increase in cytosolic Ca2+ which binds to PKC, leading it to bind to DAG, activating PKC.
IP3
24
Target of G-proteins. It cleaves a membrane phospholipid called Phosphatidyl inositol 4,5-biphosphate (PIP2), a component of the plasma membrane. DAG and IP3 are produced from PIP2 cleavage.
Phospholipase C
24
Steroid Family Examples
testosterone, estradiol, progesterone, cortisol, aldosterone.
25
Consist of a, b, and g subunits, and function the same way as the Gs type.
Ga-q subunits
27
Alpha subunit activated by binding of GTP.
GCPR Activation, 2nd Step
28
GPCRs that bind to specific ligands to regulate metabolic processes. 3 types, a1, a2, and B (1, 2, 3)
Adrenergic Receptors
28
A protein kinase that is activated by RAS-Raf that affects cell division, survival, and gene expression.
MAPK
29
Diabetes, Type I (Autoimmune)
Insulin-producing cells of the pancre as are lost. Signal (insulin) never reaches target cells
30
Ga-q subunits
Consist of a, b, and g subunits, and function the same way as the Gs type.
32
the activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP). Increasing concentrations of cAMP can activate PKA, which phosphorylates other proteins.
cAMP-dependent pathway
34
testosterone, estradiol, progesterone, cortisol, aldosterone.
Steroid Family Examples
36
Reacts with NO at an iron in its active site to initiate the signal for relaxation in smooth muscle.
cGMP
37
Steroid Hormones
hydrophobic (uncharged) ligands derived from cholesterol with characteristic 4-ring structure. Diffuse across cell membrane without transporter. Require carrier protein in bloodstrea,.
38
cAMP binds to PKA to stimulate a protein cascade.
GCPR Activation, 5th Step
38
Intracellular Ca2+
Activates PKC and Calmodulin
40
A single cell in a mixed population secretes ligands that baind only to other phenotypically different cells.
Paracrine
41
cAMP
increases the kinase activity of Protein Kinase A (PKA) by binding its two regulatory subunits.
41
Protein kinase C (PKC)
phosphorylates a variety of intracellular proteins. Activated when intracellular Ca2+ binds to it, causing it to hook up with DAG where it is thus activated.
43
Combination of long and short distance signaling
Neuronal
44
an enzyme that removes a phosphate group from its substrate
Phosphatase
44
levels of cAMP
dependent on the relative balance between adenylate cyclase and cAMP phosphodiesterase.
45
GCPR Activation, 4th Step
ATP converted into cAMP.
47
a2 receptor (inhibits AC)
G-alpha-1 receptor
48
inhibits the enzyme adenylate cyclase
Ga-i
49
Varied family of signaling molecules, wide range in size from a few to 100+ amino acids. E.g., insulin, glucagon, vascular endothelial growth factor.
peptides
50
Phospholipase C
Target of G-proteins. It cleaves a membrane phospholipid called Phosphatidyl inositol 4,5-biphosphate (PIP2), a component of the plasma membrane. DAG and IP3 are produced from PIP2 cleavage.
50
CaM-kinase II
Ca2+/Calmodulin wraps around it and initiates a phosphorylation cascade.
51
activates the enzyme phospholipase C
Ga-q
52
phosphorylates a variety of intracellular proteins. Activated when intracellular Ca2+ binds to it, causing it to hook up with DAG where it is thus activated.
Protein kinase C (PKC)
54
bind to carrier proteins outside of the cell but diffuse across plasma membrane to enter cell. Binding to ligand to receptor protein occurs inside cell.
Hydrophobic signaling molecules
54
dependent on the relative balance between adenylate cyclase and cAMP phosphodiesterase.
levels of cAMP
54
peptides
Varied family of signaling molecules, wide range in size from a few to 100+ amino acids. E.g., insulin, glucagon, vascular endothelial growth factor.
55
endocrine signaling
Signaling molecules are secreted by special cells and carried through circulation to act at distant sites.
56
GCPR Activation, 1st Step
Ligand bind to receptor on surface of cell, stimulating alpha subunit.
57
A prodrug that undergoes a chemical conversion within the body to produce NO, resulting in the dilation of blood vessels in the heart. Production of NO does not involve NO synthase.
Nitroglycerin
58
guanylyl cyclase
An important second messenger that internalizes the message carried by intercellular messengers such as peptide hormones and NO by synthesizes cGMP from GTP. It can also function as an autocrine signal.
59
cAMP-dependent pathway
the activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP). Increasing concentrations of cAMP can activate PKA, which phosphorylates other proteins.
61
Paracrine
A single cell in a mixed population secretes ligands that baind only to other phenotypically different cells.
62
Contact-dependent signaling
a type of cell signalling in that requires close contact. Plays a role in embryogenesis. A means of cell-cell recognition between cells of the same tissue. Restrains cell growth, and loss is common feature of cancer.
62
Nitroglycerin
A prodrug that undergoes a chemical conversion within the body to produce NO, resulting in the dilation of blood vessels in the heart. Production of NO does not involve NO synthase.
63
Ligand bind to receptor on surface of cell, stimulating alpha subunit.
GCPR Activation, 1st Step
65
Activates PKC and Calmodulin
Intracellular Ca2+
66
GCPR Activation, 3rd Step
Activated alpha subunit separates from the b/g subunits and stimulates Adenylate Cyclase (AC).
67
a1 receptor (stimulates Phospholipase C)
G-alpha-q receptor
69
hydrophobic (uncharged) ligands derived from cholesterol with characteristic 4-ring structure. Diffuse across cell membrane without transporter. Require carrier protein in bloodstrea,.
Steroid Hormones
70
RTK Signaling
Growth factor binds, causing two monomeric receptors to dimerize. Tyrosine residues on cytoplasm side are trans-autophosphorylated, which alters charge and conformation, creating a new binding site. GRB2 binds at an SH2 domain, recruiting SOS from the cytoplasm to the membrane. SOS binds and stimulates RAS to exchange GDP for GTP, which activates RAS. RAS activates Raf, a kinase that begins a phos-cascade known as MAPK.
72
increases the kinase activity of Protein Kinase A (PKA) by binding its two regulatory subunits.
cAMP
74
hydrophilic ligand binds to its transmembrane receptor outside cell. Receptor alterationdelivers signal into cell via intracellular proteins.
Cell-Surface Receptors
75
Insulin is made but target cells become less responsive to ligand binding. Eventually, pancreas synthesis of insulin decreases (B-cell exhaustion).
Diabetes, Type II (Insulin-Resistant Diabetes)
76
G-alpha-s receptor
All gamma (B) (1, 2, and 3) receptors. (stimulates AC)
78
Cholera toxin
A toxin that ADP-ribosylates the Ga-s subunit in the cytoplasm. As a result, Ga-s cannot hydrolyze GTP, leading to constant signaling of AC and production of cAMP.
80
endocrine gland examples
pituitary, thyroid, parathyroid, pancreas, adrenal glands, and gonads.
81
Autocrine
A single cell in a mixed population secretes ligands that bind only to its OWN receptor. Or in a group of identical cells, secreted ligands bind receptors on adjacent cells
82
Nitric oxide
Intracellular ligand synthesized from the amino acid arginine. Soluble in both aqueous and lipid media, and readily diffuses through cytoplasm and plasma membranes. Half-life of only a few seconds, can only effect nearby cells.
83
Formed from PIP cleavage, remains in the membrane.
DAG
84
Neuronal
Combination of long and short distance signaling
85
Kinase proteins
Can transfer the terminal phosphate from ATP to the hydroxyl group of a serine, threonine, or tyrosine residue within a protein. Stay active after phosphorylation event, leading to signal amplification.
86
Pertussis Toxin
A toxin covalently adds an ADP-ribose to the Ga-i subunit. Inhibited Ga-I cannot inhibit AC, so cAMP levels increase.
87
Ga-s
activates the enzyme adenylate cyclase
89
Transmembrane proteins that can bind ligand on their extracellular portion and phosphorylate intracellular signaling molecules with the tyrosine kinase activity of their cytoplasmic domain.
Receptor Tyrosine Kinases (RTKs)
90
Can transfer the terminal phosphate from ATP to the hydroxyl group of a serine, threonine, or tyrosine residue within a protein. Stay active after phosphorylation event, leading to signal amplification.
Kinase proteins
92
a covalent modification that requires the action of an enzyme to either form a new phosphate bond or break it. Rapid process with a "domino effect".
Phosphorylation
93
pituitary, thyroid, parathyroid, pancreas, adrenal glands, and gonads.
endocrine gland examples
94
Ca2+/Calmodulin wraps around it and initiates a phosphorylation cascade.
CaM-kinase II
95
Phosphorylation
a covalent modification that requires the action of an enzyme to either form a new phosphate bond or break it. Rapid process with a "domino effect".
96
GCPR Activation, 5th Step
cAMP binds to PKA to stimulate a protein cascade.
97
Adrenergic Receptors
GPCRs that bind to specific ligands to regulate metabolic processes. 3 types, a1, a2, and B (1, 2, 3)
98
Steroid Hormone Mechanism
Hormone binds to its receptor in the cytoplasm, causing receptor/ligand complex to translocate to the nucleus, which binds to DNA sequence upstream of ligand-responsive genes, stimulating DNA transcription, thus synthesizing new protein.
99
An enzyme that converts arginine to nitric oxide and citrulline.
NO synthase (NOS)
100
Signaling By Nitric Oxide
1. release of acetylcholine from the nerve terminus of a blood vessel. 2. Acetylcholine binds to receptors on the surface of endothelial cells of the blood vessel wall initiating a signalling cascade that activates an enzyme that converts arginine to target molecule and citrullline. 3. __ diffuses out of endothelial cell and into smooth muscle cell. 4. __ reacts with iron in active site of guanylyl cyclase, stimulating the production of cyclic GMP.5. cGMP initiates a signaling cascade leading to rapid relaxation of smooth muscle cell.
101
Autocrine + Paracrine
Signaling over short distances
102
NO synthase (NOS)
An enzyme that converts arginine to nitric oxide and citrulline.
103
G-alpha-q receptor
a1 receptor (stimulates Phospholipase C)
104
Receptor Tyrosine Kinases (RTKs)
Transmembrane proteins that can bind ligand on their extracellular portion and phosphorylate intracellular signaling molecules with the tyrosine kinase activity of their cytoplasmic domain.
105
Ca2+-ATPase
can lower cytoplasmic calciumlevels by pumping calcium back into the ER (primary active transport)
107
All gamma (B) (1, 2, and 3) receptors. (stimulates AC)
G-alpha-s receptor
108
activates the enzyme adenylate cyclase
Ga-s
109
1. Signaling through the neuron via an electrical potential 2. 2. Signaling to the target cell through the action of a neurotransmitter released at the synapse.
Neuronal Signaling Phases
111
Signaling molecules are secreted by special cells and carried through circulation to act at distant sites.
endocrine signaling
112
cAMP phosphodiesterase
Converts cAMP to the low-energy nucleotide AMP (adenosine monophosphate).
113
transmembrane protein receptors that that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses.
G-protein coupled receptor (GPCR)
114
a type of cell signalling in that requires close contact. Plays a role in embryogenesis. A means of cell-cell recognition between cells of the same tissue. Restrains cell growth, and loss is common feature of cancer.
Contact-dependent signaling
115
ADP ribosylase
covalently adds an ADP-ribose group to an arginine residue og G-alpha subnits.
116
MAPK
A protein kinase that is activated by RAS-Raf that affects cell division, survival, and gene expression.
117
Activated when bound to Ca2+. When activated, wraps around other proteins, changing their conformation.
Calmodulin
118
ATP converted into cAMP.
GCPR Activation, 4th Step
