Biochemistry - Signal Transduction Flashcards
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.
guanylyl cyclase
can lower cytoplasmic calcium levels by pumping calcium back into the ER (primary active transport)
Ca2+-ATPase
Ga-i
inhibits the enzyme adenylate cyclase
Kinase Targets
other kinases, phophotases, metabolic enzymes, transcription factors.
Signaling over long distances
Endocrine
- 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.
Signaling By Nitric Oxide
G-protein coupled receptor (GPCR)
7 member transmembrane protein receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses.
A toxin covalently adds an ADP-ribose to the Ga-i subunit. Inhibited Ga-i cannot inhibit AC, so cAMP levels increase.
Pertussis Toxin
Hydrophobic signaling molecules
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.
Cell-Surface Receptors
hydrophilic ligand binds, alteration delivers signal into cell via intracellular proteins.
Calmodulin
Activated when bound to Ca2+. When activated, wraps around other proteins, changing their conformation.
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.
RTK Signaling
Neuronal Signaling Phases
- Signaling through the neuron via an electrical potential 2. Signaling to the target cell through the action of a neurotransmitter released at the synapse.
covalently adds an ADP-ribose group to an arginine residue og G-alpha subnits.
ADP ribosylase
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.
Cholera toxin
cGMP
Reacts with NO at an iron in its active site to initiate the signal for relaxation in smooth muscle.
Signaling over short distances
Autocrine + Paracrine
Insulin-producing cells of the pancre as are lost. Signal (insulin) never reaches target cells
Diabetes, Type I (Autoimmune)
G-alpha-1 receptor
a2 receptor (inhibits AC)
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.
Steroid Hormone Mechanism
Ga-q
activates the enzyme phospholipase C
Activated alpha subunit separates from the b/g subunits and stimulates Adenylate Cyclase (AC).
GCPR Activation, 3rd Step
Phosphatase
an enzyme that removes a phosphate group from its substrate
DAG
Formed from PIP cleavage, remains in the membrane.
GCPR Activation, 2nd Step
Alpha subunit activated by binding of GTP.
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).
Endocrine
Signaling over long distances
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.
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
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
other kinases, phophotases, metabolic enzymes, transcription factors.
Kinase Targets
Converts cAMP to the low-energy nucleotide AMP (adenosine monophosphate).
cAMP phosphodiesterase
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
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
Steroid Family Examples
testosterone, estradiol, progesterone, cortisol, aldosterone.
Consist of a, b, and g subunits, and function the same way as the Gs type.
Ga-q subunits
Alpha subunit activated by binding of GTP.
GCPR Activation, 2nd Step
GPCRs that bind to specific ligands to regulate metabolic processes. 3 types, a1, a2, and B (1, 2, 3)
Adrenergic Receptors
A protein kinase that is activated by RAS-Raf that affects cell division, survival, and gene expression.
MAPK
Diabetes, Type I (Autoimmune)
Insulin-producing cells of the pancre as are lost. Signal (insulin) never reaches target cells
Ga-q subunits
Consist of a, b, and g subunits, and function the same way as the Gs type.
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
testosterone, estradiol, progesterone, cortisol, aldosterone.
Steroid Family Examples
Reacts with NO at an iron in its active site to initiate the signal for relaxation in smooth muscle.
cGMP
Steroid Hormones
hydrophobic (uncharged) ligands derived from cholesterol with characteristic 4-ring structure. Diffuse across cell membrane without transporter. Require carrier protein in bloodstrea,.
cAMP binds to PKA to stimulate a protein cascade.
GCPR Activation, 5th Step
Intracellular Ca2+
Activates PKC and Calmodulin
