BERNSTEIN PHSC 2301 Signal Transduction

during evolution, unicellular organisms developed mechanisms to respond to physical and chemical signals and developed mechanisms to interact with other cells (true or false)

true

bacteria used quorum sensing to coordinate spore formation, antibiotic production, conjugation, and motility (true or false)

true

in yeasts, proteins were identified, providing signal network including cell-surface receptors, G-proteins, and protein kinases (true or false)

true

human genome has more than 1500 genes only encoding receptor proteins (true or false)

true

process of information transfer mediated by extracellular/intracellular signals

signal transduction

signal transduction process initiates intracellular signaling process with a physiological change. ____________ rapidly and transiently increase concentration inside the cell

second messengers

about 200 types of human cells characterized by particular signaling components (true or false)

true

what are characterized by an enormous diversification

signaling pathways

all signaling proteins exist in only one form (true or false)

false (exists in a multiplicity of different isoforms)

father of modern pharmacologyy that introduced the concept of a "magic bullet" aka drug as well as receptor

Ehrlich

receptors have low affinity (true or false)

false (it has very high affinity)

extracellular signal may be detected at what

10^-8 M

four types of signaling

contact-dependent, paracrine, synaptic, endocrine

type of signaling:

require cells to be in a direct membrane-membrane contact

contact-dependent

type of signaling:

signals released and act upon neighboring cells

paracrine

type of signaling:

signals release in the synaptic space

synaptic

type of signaling:

endocrine cells release signals operating through the whole organism

endocrine

signals can only operate at short distances (true or false)

false (can operate at short or long distances or both)

cells respond to a specific combination of signal molecules (true or false)

true

signal molecules may operate in innumerable combinations but cells respond in a specific fashion obtained through evolution (true or false)

true

mechanical forces, osmolarity, temperature, and light are other signals cells may respond to (true or false)

true

approximately 25 different families of receptors, families share one or more homologous domains

plasma membrane receptors

plasma membrane receptors are capable to detect and respond to myriad of chemical and physical stimuli. _____________ evolution resulted in multiple receptor isoform that reacts to different ligands

divergent

original concept of drug ligand receptor relationship:

drugs bind to any receptor and individual receptors recognize different classes of drugs (true or false)

false (drugs bind only to certain receptors and individual receptors recognize only certain class of drugs (ligands)

new concept of drug ligand receptor relationship:

no drug is completely specific in its action; one ligand activates multiple signal pathways and multiple ligands can result in activation of the same pathway

one component of the pathway can regular components of different pathways (true or false)

true

there can be resistance to ligands due to change in the receptors, loss of receptors, exhausting of mediators, increased __________________-, and physiological adaptation

metabolic degradation

increase sensitivity to drug

receptor upregulation

decrease sensitivity to drug

receptor down regulation

in early theory, drugs (ligands) bind only to certain receptors (true or false)

true

in early theory, individual receptors recognize only certain class of drugs (ligands) (true or false)

true

in reality - no drug (ligand) is completely specific in its action (true or false)

true

in reality - one ligand activates one signal pathway (true or false)

false (one ligand activates many pathways)

in reality, one component of the pathway can regulate components of different pathways and multiple ligands can result in activation of the same pathway (true or false)

true

what are the receptors superfamilies and signal transduction

steroid receptor signal, transmembrane receptor proteins, ion channel-linked receptors, g-protein-coupled receptors

type of receptors superfamilies:

lipid-soluble signal transduction; receptors for steroids that are located in the cytoplasm or in the nucleus

steroid receptor signal

steroid hormone receptors act as _____________ transcriptional factor

since hormones bind to receptors, they can bind to DNA and regulate transcription (RNA production) for a specific gene

ligand-activated

_____________ includes steroids - cortisol, progesterone, estradiol, testoerone, and retinoid acid

hormones

steroid receptor signal:

1. steroid hormone crosses the ____________

2. steroid hormon binds with the ______________ receptor

3. transport into the _________

4. hormone affects hormone response element

membrane, intracellular, nucleus

two major mechanisms of lipid-soluble signal trasnduction

NISS and MISS

NISS (nuclear initiated steroid signaling):

steroid ligands diffuses through the membrane and binds to soluble receptors in cytoplasm or nucleus then activates nuclear DNA ligand bonding domain which is the ___________________, gene activation depends upon cell type and a nature of a ligand

hormone response element

what type of steroid ligands are these:

corticosteroids, mineralocorticoids, sex steroids

type I

what type of steroid ligands are these:

vitamin A, vitamin D, retinoid, and thyroid hormones

type II

what are the two types of binds in NISS

type I receptor and type II receptors

what acts as a ligand activated transcription factor aka a "gene-active" receptor

hormone response elements

hormone response element's action time is

(big minutes) hours-days

effect of nuclear initiated steroid signaling may last for how long

hours-days

MISS (membrane initiated steroid signaling)

membrane receptors located on the _______________ surface in caveola (depression), rapid effect due to action upon steroid receptor on plasma membrane, induces biological effects faster than classical NISS, membrane receptors have the same proteins structure as intracellular steroid receptors

outer membrane

MISS has a ________ effect due to action upon steroid receptors on plasma membrane

rapid

NISS is faster than MISS (true or false)

false

steroid signaling pathway affects what major parts of the cell

cytoplasm, nucleus, membrane

rapid biological responses to steroid signaling pathways include ion channels, transcription, translation, and provides a general biological response to the steroid hormone (true or false)

true

type of receptors superfamilies:

kinase-linked receptors

transmembrane receptor protein

ligands for transmembrane receptor proteins include

insulin and pharmacological agents

common architecture of the receptor in transmembrane receptor protein is a large ___________ binding domain

extracellular

transmembrane receptor proteins have cytoplasmic enzyme domains like tyrosine kinase, serine kinase, or guanylyl cyclase (true or false)

true

transmembrane receptor proteins are involved in ___________- and differentiation, indirectly controls gene

cell growth

what is an example of a transmembrane receptor protein?

insulin receptor

insulin receptor:

specific receptor - transmembrane glycoprotein

receptors consists of _____ alpha and _____ beta subunits

2, 2

alpha and beta subunits in an insulin receptor are linked by what type of bonds

disulfide

what type of subunit is explained:

entirely extracellular (ligand-binding site)

alpha

what type of subunit is explained

inside

transmembrane proteins with tyrosine-kinase activity

beta

type of receptors superfamilies:

ionotropic; ligand/voltage-gated channels

ion channel linked-receptors

ion channel linked-receptors involve many useful drugs affecting Ach, serotonin, GABA, and glutamate receptors (true or false)

true

ion channel linked-receptors are involved in ______ synaptic transmissions (ms-s) and affect electrical potential across the membrane

fast

ion channel linked receptors has how many subunits

five

what are the subunits in ion channel linked receptors

two alpha, one beta, one gamma, and one sigma

cylindrical structure of the ion channel linked-receptors is about what in diameter

8nm

2 Ach bind to the extracellular domain of two ______ subunits in ion channel linked receptors

alpha

conformational change and receptor opens a central _______________ ion channel

transmembrane

type of receptors superfamilies:

metabotropic

protein-coupled receptors

ligands in _________________ receptors

epinephrine, norepinephrine, opioids, and many pharmacological agents

protein-coupled

protein-coupled receptors are involved in ________ synaptic transmissions

fast

largest family of the cell surface receptors

protein coupled receptors

all of the protein coupled receptors evolved from a common evolutionary precursor (true or false)

true

g proteins are similar to molecular _________

switches

typical g protein signal transduction

1. ligand affect the receptor

2. _______________ changes in the receptor

3. activation of _________________

4. activated alpha subunits separates and moves laterally toward adenylate cyclase

5. activation of adenylate cyclase

6. AC activated transformation of _______ to ________

7. cAMP activates protein kinase

8. protein kinase activates and opens _________ channels

9. calcium ions diffuse into the ___________

10. multiple physiological and biochemical changes

conformation, Gs-protein, ATP, cAMP. calcium, cytoplasm

Gs (stimulatory) has receptors of beta-adrenergic glucagon, serotonin

________ AC which _______ cAMP which ___________ protein kinase which __________ calcium ion channel

increase, increase, increase, opens

Gi1 Gi2 Gi3 (inhibitory) has receptors of Ach and opioids

_________ AC which _______ cAMP and __________ potassium channels

decrease, decrease, increase

Golf (olfaction) has receptors of odorants (olfactory epithelium)

_________ AC which ________ cAMP

increase, increases

Gq has receptors of Ach, bombesin, 5-HT2

__________ phospholipase C which ________ IP3 and __________ calcium 2+ ion

increase, increase, increase

Gt1 and Gt2 has receptors of photon (rods and cones)

_____________ cGMP PD which ___________ cGMP

increase, decrease

membrane bound enzyme that produces cAMP

adenylate cyclase

adenylate cyclase requires _____ concentration of ATP and resembles certain channel proteins

low

a universal second messenger and is a major intracellular target - protein kinase A

cyclic AMP (cAMP)

increase of cAMP produces different effects in different cells (true or false)

true

what converts cAMP to 5'-AMP

enzyme phosphodiesterase

to raise concentration of cAMP, use phosphodiesterase inhibitor (true or false)

true

second messenger for adenylate cyclase is _________ and the protein kinase is _________

cAMP, PKA

second messenger for guanylate cyclase is _______ and the protein kinase is ______

cGMP, PKG

second messenger for phospholipase C is ________ and the protein kinase is _____

DAG, PKC

protein phosphorylation controls function fo __________ proteins

intracellular

there are many phosphokinases but with the same specificity for the substrate (true or false)

false (different specificity for the substrate)