Signal Transduction, Membrane Receptors, Second Messengers, and Regulation of Gene Expression Flashcards
Antithrombotic drug that inhibits 💡cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2)💡
ASPIRIN
Increase 💡cardiac contractility and 💡heart rate in patients with low blood pressure
β1-Agonists
💡Dilate bronchi and are used to treat 💡asthma and chronic obstructive lung disease.
β2-Agonists
Used to treat 💡hypertension, angina, cardiac arrhythmias, and congestive heart failure
β-adrenergic antagonists
An 💡antidepressant medication that 💡inhibits reuptake of the neurotransmitter 💡serotonin into the presynaptic cell
Fluoxetine (Prozac)
A 💡monoclonal antibody used to treat 💡metastatic breast cancer in women who overexpress 💡HER2/neu
Trastuzumab (Herceptin)
💡Monoclonal antibodies that are used to treat 💡metastatic colorectal cancer and 💡cancers of the head and neck.
These antibodies bind to and 💡inhibit the EGF receptor and thereby inhibit EGF-induced cell growth in cancer cells.
Cetuximab (Erbitux) and bevacizumab (Avastin)
Drugs that 💡inhibit cyclic guanosine monophosphate (cGMP)–specific phosphodiesterase type 5, prolong the 💡vasodilatory effects of nitric oxide and are used to treat 💡erectile dysfunction and pulmonary arterial hypertension
Sildenafil (Viagra), Tadalafil (Cialis), and Vardenafil (Levitra)
How Cells Communicate
💡💡 Ligand Receptor Signaling proteins Target proteins Effect
A signaling molecule (i.e., hormone or neurotransmitter) binds to a receptor, which may be in the plasma membrane, cytosol, or nucleus. Binding of ligand to a receptor activates intracellular signaling proteins, which interact with and regulate the activity of one or more target proteins to change cellular function. Signaling molecules regulate cell growth, division, and differentiation and influence cellular metabolism. In addition, they modulate the intracellular ionic composition by regulating the activity of ion channels and transport proteins. Signaling molecules also control cytoskeleton-associated events, including cell shape, division, and migration and cell-to-cell and cell-to-matrix adhesion
Signaling pathways are characterized by:
(1) multiple, hierarchical steps;
(2) amplification of the signal-receptor binding event, which magnifies the response;
(3) activation of multiple pathways and regulation of multiple cellular functions
(4) antagonism by constitutive and regulated feedback mechanisms,
Secretion of signaling molecules is?
Cell-type Specific
In which a 💡membrane-bound signaling molecule of one cell binds directly to a 💡plasma membrane receptor of another cell.
Important during development, in immune responses, and in cancer
Contact-Dependent Signaling
Are released by 💡one type of cell and 💡act on another type
Usually taken up and degraded by enzymes.
Ex. Enterochromaffin-like cells
PARACRINE SIGNALS
Involves the release of a molecule that affects the 💡same cell or other cells of the 💡same type
Occurs at 💡short distances
Example: Cancer cell, insulin release by the beta cells of the pancrease
Autocrine Signaling
💡Neurons transmit electrical signals along their axons and release neurotransmitters at synapses that affect the function of other neurons or cells that are distant from the neuron cell body
Synaptic Signaling
Are 💡hormones that are secreted into the blood and are widely dispersed in the body
Occurs over 💡long distances
Relatively 💡slow compared to the synaptic signaling
ENDOCRINE SIGNALS
Specialized junctions that allow intracellular signaling molecules, generally less than 1200 D in size, to diffuse from the cytoplasm of one cell to an 💡adjacent cell.
Gap Junctions
It regulates the 💡permeability of gap junctions
💡 C H Cyclic MP
Cytosolic Ca2+, H+
Cyclic adenosine monophophate (cAMP)
Membrane Potentials
All signaling molecules bind to specific receptors that act as (1)__, thereby converting a (2)__ into intracellular signals that affect cellular function.
💡💡
ST
LRBE
(1) SIGNAL TRANSDUCERS
(2) LIGAND-RECEPTOR BINDING EVENT
4 Basic Classes of Membrane Receptors
💡💡 L G E N
(1) ligand-gated ion channels,
(2) G protein–coupled receptors (GPCRs),
(3) enzyme-linked receptors,
(4) nuclear receptors
Mediate 💡direct and 💡rapid synaptic signaling between 💡electrically excitable cells
A membrane receptors that has direct and rapid synaptic signaling between electrically excitable cells.
This class of receptors transduces a 💡chemical signal into an 💡electrical signal, which elicits a response
Predominates in the nervous system mediating fast
excitatory or inhibitory neurotransmission.
Ligand-Gated Ion Channels/Ionotrophic
Or
Voltage-gate; Stretch- activated; and Temperature-gated.
Regulate the 💡activity of other proteins, such as enzymes and ion channels
Membrane receptors that influence the activity of cells 💡indirectly, with the transduction of an extracelular signal (ligand binding) to an intracellular one and the activation of secondary molecules.
G PROTEIN-COUPLED RECEPTORS/Metabotropic
Either 💡function as enzymes or are associated with and 💡regulate enzymes
Single pass transmembrane proteins, with extracellular and intracellular domains.
ENZYME-LINKED RECEPTORS
💡Small hydrophobic molecules that diffuse across the plasma membrane, and bind to nuclear receptors or to cytoplasmic receptors that, once bound to their ligand, translocate to the nucleus
Nuclear Receptors
Intracellular/steroid receptor
Elaborates a 💡cytosolic peptide fragment that enters the nucleus and regulates gene expression
In this signaling pathway, binding of ligand to a plasma membrane receptor leads to 💡ectodomain shedding, facilitated by members of the metalloproteinase-disintegrin family, and produces a carboxy-terminal fragment that is the substrate for 💡γ-secretase causing the 💡release of an intracellular domain of the protein that enters the nucleus and regulates transcription
Example: Sterol Regulatory Element–Binding Protein (SREBP)
Regulated Intramembrane Proteolysis (RIP)
💡Induces RIP causing the 💡release of an intracellular domain of the protein that enters the nucleus and regulates transcription
γ-Secretase
A progressive neurodegenerative brain disease characterized by the formation of 💡amyloid plaques [💡amyloid β-protein (Aβ)]
ALZHEIMER’S DISEASES
Intracellular signaling molecule
Function: Amplify, terminate thru enzymes, specific, diverse
Examples: cAMP, cGMP, Ca++, and diacylglycerol
SECOND MESSENGERS
The 💡first messenger of the signal that 💡binds to the receptor.
LIGAND
Intracellular signaling proteins that 💡relay the signal by passing the message directly to another protein
REVERSIBLE MOLECULAR SWITCHES
Cells can also adjust their sensitivity to a signal by? Whereby 💡prolonged exposure to a hormone decreases the cell’s response over time. But is a 💡reversible prcess.
DESENSITIZATION
Involves a 💡reduction in the response 💡only to the signaling molecule that caused the response.
Homologous Desensitization
Is when 💡one ligand desensitizes the response to 💡another ligand
Heterologous Desensitization
Binding of GTP (1)__, whereas hydrolysis of GTP to GDP (2)__, GTP-binding proteins.
(1) ACTIVATES
(2) INACTIVATES
