Lecture #23

Question 1

________ messenger molecules transmit messages between cells

Answer 1

Extracellular

Question 2

______ → the cell has receptors on its surface that respond to the messenger
_______→ messenger molecules travel short distances through extracellular space.
_______ → messenger molecules reach their target cells through the bloodstream.

Answer 2

Autocrine, Paracrine, Endocrine

Question 3

_______ on or in target cells receive an extracellular message

Answer 3

Receptors

Question 4

______ – molecule that binds to the receptor

Answer 4

Ligand

Question 5

______ _______: small intracellular mediator. Small intracellular signaling molecule that is formed or released foraction in response to an extracellular signal and helps to relay the signal within the cell.

Answer 5

Second messenger

Question 6

Each cell _____ displays a set of receptors

Answer 6

type

Question 7

Various responses induced by the same ____________, acetylcholine depending on the cell type.

Answer 7

neurotransmitter

Question 8

Target cells can become __________ (adapted) to an extracellular signal molecule

Answer 8

desensitized

Question 9

_______ add phosphate groups while phosphatases remove them

Answer 9

Kinases

Question 10

Protein phosphorylation can change protein behavior in different ways by:
- activating or inactivating an _______.
- increasing or decreasing _______-protein interactions.
- changing the subcellular location of the ________.
- triggering protein ________.

Answer 10

enzyme, protein, protein, degradation

Question 11

Extracellular messengers include:
- ______ molecules such as amino acids and their derivatives (e.g., acetylcholine, epinephrine, dopamine).
- _____ such as NO and CO.
- _______, derived from cholesterol.
- _______, derived from arachidonic acid.
- Various _______ and proteins.

Answer 11

Small, Gases, Steroids, Eicosanoids, peptides

Question 12

Receptor types include:
- ______ gated channels (ion-channel-coupled receptors).
- ___-protein coupled receptors (GPCRs).
- ______-coupled receptors (Receptor protein-tyrosine kinases (RTKs)).

Answer 12

Ligand, G, Enzyme

Question 13

What kind of signaling complex does this describe?

A receptor and some of the intracellular signaling proteins it activates in sequence are preassembled into a signaling complex on the inactive receptor by a large scaffold protein.

Answer 13

Performed Signaling Complex on a Scaffold Protein

Question 14

What kind of signaling complex does this describe?

A signaling complex assembles transiently on a receptor only after the binding of an extracellular signal molecule has activated the receptor. Here, the activated receptor phosphorylates itself at multiple sites, which then act as docking sites for intracellular signaling proteins.

Answer 14

Assembly of Signaling Complex on an Activated Receptor

Question 15

What kind of signaling complex does this describe?

Activation of a receptor leads to the increased phosphorylation of specific phospholipids (phosphoinositides) in the adjacent plasma membrane. Docking sites for specific intracellular signaling proteins, which can now interact with each other.

Answer 15

Assembly of Signaling Complex on Phosphoinositide Docking Sites

Question 16

What is the largest superfamily of proteins encoded by animal genomes (1000s)?

Answer 16

G-protein-coupled receptors

Question 17

Natural ligands that bind to GPCRs: ?

Answer 17

Hormones, Neurotransmitters, Opium derivatives, Chemoattractants

Question 18

______ activate receptors that stimulate effectors to give rise to a physiological response

Answer 18

Ligands

Question 19

A GDP is exchanged for ____ on the Ga subunit, thus activating it and promoting association with the effector. Ga dissociates and binds to the _______

Answer 19

GTP, effector

Question 20

Ga subunits can turn themselves off by _______ of GTP to GDP and Pi.

Answer 20

hydrolysis

Question 21

___________ G proteins function as molecular timers, and while active, Ga subunits can turn on downstream effectors

Answer 21

Heterotrimeric

Question 22

Heterotrimeric G proteins come in four varieties:
1. ___family members couple receptors to adenylyl cyclase.
2. ___ family members contain Ga subunits that activate PLCb.
3. ___ subunits function by inhibiting adenylyl cyclase.
4. ___ members are less well characterized.

Answer 22

Gs, Gq, Gi, G12/13

Question 23

Phosphorylation of the GPCRs by G protein-coupled receptor kinase sets the stage for the binding of _______ (complete for binding with the G proteins)

Answer 23

arrestins

Question 24

Upon arrestin binding GPCRs become __________. If receptors are recycled and returned to the cell surface the cells remain sensitive to the ligand and are said to be __________.

Answer 24

desensitized, resensitized

Question 25

Cyclic AMP is a ______ messenger that diffuses to other sites in the cell.

Answer 25

second

Question 26

The synthesis of cyclic AMP follows the binding of a _____ messenger, a hormone or other ligand, to a receptor at the outer surface of the cell

Answer 26

first

Question 27

_______ messengers enable cells to mount a large-scale, coordinated response following stimulation by a single extracellular ligand

Answer 27

Second

Question 28

Some phospholipids of cell membranes are converted into second messengers by phospholipases (lipid-_______), phospholipid kinases (lipid-__________), and phospholipid phosphatases (lipid-____________)

Answer 28

splitting, phosphorylating, dephosphorylating

Question 29

Phosphatidylinositol-specific phospholipase C-b produces ______ messengers derived from phosphatidylinositol-inositol triphosphate (IP3) and diacylglycerol (DAG)

Answer 29

second

Question 30

DAG activates protein ______ C, which phosphorylates serine and threonine residues on target proteins

Answer 30

kinase

Question 31

GPCRs are capable of binding a _____ array of ligands

Answer 31

diverse

Question 32

Receptor ______ can have different affinities for a ligand or may interact with different types of G proteins

Answer 32

isoforms

Question 33

Heterotrimeric G proteins and effectors can also have different ________

Answer 33

isoforms

Question 34

The ______ stimulus can activate a stimulatory G protein (Gas) in one cell and an inhibitory G protein (Gai subunit) in a different cell

Answer 34

same

Question 35

GPR124 regulates specifically ______ blood vessels formation

Answer 35

brain

Question 36

Protein-tyrosine _______, which phosphorylate tyrosine residues on target proteins, can be divided in two groups

Answer 36

kinases

Question 37

Protein-tyrosine kinases can be divided in two groups:
_______ protein‐tyrosine kinases (RTKs).
____-_______ (or cytoplasmic) protein‐tyrosine kinases.

Answer 37

Receptor, Non‐receptor

Question 38

RTKs are activated _______ by extracellular growth and differentiation factors

Answer 38

directly

Question 39

Non-receptor protein-tyrosine kinases are regulated ________ by extracellular signals

Answer 39

indirectly

Question 40

Two mechanisms for receptor dimerization:
_______-mediated dimerization (e.g., PDGF)
_______-mediated dimerization (e.g., EGF).

Answer 40

ligand, receptor

Question 41

For most RTKs, dimerization brings two kinase domains in close contact for ______-autophosphorylation

Answer 41

trans

Question 42

__________ sites can regulate the receptor’s kinase activity or serve as binding sites for cytoplasmic signaling molecules

Answer 42

Autophosphorylation

Question 43

Kinase activity is usually controlled by autophosphorylation on ________ residues that are present in the activation loop of the kinase domain.

Answer 43

tyrosine

Question 44

Following its phosphorylation, the activation loop is stabilized in a position _____ from the substrate-binding site, resulting in activation of the kinase domain

Answer 44

away

Question 45

The receptor subunits then phosphorylate each other on tyrosine residues that are present in regions adjacent to the ______ domain; these sites act as binding sites for cellular signaling proteins

Answer 45

kinase

Question 46

Phosphorylated tyrosines bind effector proteins that have either a ? (SH2) domain or a ________-_______ (PTB) domain

Answer 46

Src-homology 2, phosphotyrosine-binding

Question 47

SH2 and PTB domain proteins include:
1. ________ proteins that bind other proteins.
2. _______ proteins that supply receptors with other tyrosine phosphorylation sites.
3. Signaling ______ (kinases) that lead to changes in cell.
4. ________ factors.

Answer 47

Adaptor, Docking, enzymes, Transcription

Question 48

Signal transduction by RTKs is usually terminated by ___________ of the receptor, primarily through clathrin-mediated endocytosis

Answer 48

internalization

Question 49

Internalized RTKs can have several alternate fates
1. They can be degraded in ________.
2. Returned to the ______ membrane.
3. Become part of endosomal signaling complexes and engage in continued ________ signaling.

Answer 49

lysosomes, plasma, intracellular

Question 50

__________ signaling pathways activated by GPCRs, RTKs or both.

Answer 50

Intracellular