chap16 Flashcards
Cells in multicellular organisms communicate through a huge variety of _.
extracellular chemical signals
In animals, hormones are carried in the blood to distant target cells, but most other extracellular signal molecules act over only a short distance. Neighboring cells often communicate through _
direct cell-cell contact.
For an extracellular signal molecule to influence a target cell it must interact with a _ on or in the target cell. Each _ protein recognizes a _ signal molecule.
receptor protein
receptor
particular
Most extracellular signal molecules bind to cell-surface receptor proteins that _ the extracellular signal into different _ signals, which are usually organized into _ pathways.
convert (transduce)
intracellular
signaling
There are three main classes of cell-surface receptors: (1) _, (2) _, and (3) _
ion- channel-coupled receptors
G-protein-coupled receptors (GPCRs)
enzyme-coupled receptors.
GPCRs and enzyme-coupled receptors respond to extracellular signals by _, which, in turn, activate _ that _.
_
activating one or more intracellular signaling pathways
_
effector proteins
_
alter the behavior of the cell
_ signaling pathways is as important as turning them on. Each activated component in a signaling pathway must be subsequently _ for the pathway to function again.
Turning off
inactivated or removed
GPCRs activate _ called _ proteins; these act as _, transmitting the signal onward for a short period before switching _ by hydrolyzing their bound GTP to GDP.
trimeric GTP-binding proteins
G
molecular switches
themselves off
G proteins directly regulate _ or _ in the plasma membrane. Some directly activate (or inactivate) the _, which increases (or decreases) the intracellular concentration of the second messenger molecule _; others directly activate the _, which generates the second messenger molecules _ and _.
ion channels
enzymes
enzyme adenylyl cyclase
cyclic AMP
enzyme phospholipase C
inositol trisphosphate (IP3)
diacylglycerol
_ opens Ca2+ channels in the membrane of the endoplasmic reticulum, releasing a flood of free Ca2+ ions into the cytosol. The Ca2+ itself acts as a _, altering the activity of a wide range of _ proteins. These include calmodulin, which activates various target proteins such as _
IP3
second messenger
Ca2+-responsive
_
Ca2+/calmodulin-dependent protein kinases (CaM-kinases).
_
A rise in cyclic AMP activates _, while Ca2+ and diacylglycerol in combination activate _.
protein kinase A (PKA)
protein kinase C (PKC)
PKA, PKC, and CaM-kinases phosphorylate selected _ proteins on _ and _, thereby altering their activity. Different cell types contain _ sets of _ and are therefore affected in different ways.
signaling and effector
serines
threonines
different
signaling and effector proteins
Enzyme-coupled receptors have intracellular protein domains that function as _ or are _. Many enzyme-coupled receptors are _, which _ themselves and select intracellular signaling proteins on _. The phosphotyrosines on RTKs then serve as _ for various _ proteins.
enzymes
associated with intracellular enzymes
receptor tyrosine kinases (RTKs)
phosphorylate
tyrosines
docking sites
intracellular signaling
Most RTKs activate the monomeric _, which, in turn, activates a _ signaling module that helps relay the signal from the plasma membrane to the _.
GTPase Ras
three-protein MAP-kinase
nucleus
Ras mutations stimulate _ by keeping Ras (and, consequently, the Ras–MAP kinase signaling pathway) constantly _ and are a common feature of many human _.
cell proliferation
active
cancers
Some RTKs stimulate cell _ and cell _ by activating PI 3-kinase, which phosphorylates specific _ in the cytosolic leaflet of the plasma membrane lipid bilayer. This inositol _ creates lipid _ sites that attract specific signaling proteins from the cytosol, including the protein kinase Akt, which becomes active and relays the signal onward.
growth
survival
inositol phospholipids
phosphorylation
docking
Other receptors, such as Notch, have a direct pathway to the _. When activated, part of the receptor migrates from the plasma membrane to the _, where it regulates the _
nucleus
nucleus
transcription of specific genes.
Some _, such as steroid hormones and nitric oxide, are small or hydrophobic enough to cross the plasma membrane and activate _ proteins, which are usually either _ regulators or _.
extracellular signal molecules
intracellular
transcription
enzymes
Plants, like animals, use enzyme-coupled cell-surface receptors to recognize the extracellular signal molecules that control their _ and _; these receptors often act by _ of specific genes.
growth
development
relieving the transcriptional repression
Different intracellular signaling pathways _, enabling each cell type to produce the appropriate response to a combination of _. In the absence of such signals, most animal cells have been programmed to _
interact
extra-cellular signals
kill themselves by undergoing apoptosis.
Animal cells use extracellular signal molecules to communicate with one another
in various ways:
endocrine signals
Paracrine signals
Neuronal signals
contact-dependent signaling
Hormones produced in _ glands are secreted into the bloodstream and
are distributed widely throughout the body.
endocrine
_ signals are released by cells into the extracellular fluid in their neighborhood and act locally.
Paracrine
In contact-dependent signaling, a cell-surface-bound _ binds to a _ on an _ cell. Many of the same types of signal molecules are used for endocrine, paracrine, and neuronal signaling. The crucial differences lie in the _ and _ with which the signals are delivered to their targets.
signal molecule
receptor protein
adjacent
speed
selectivity
responses—such as _—need not involve changes in gene expression and therefore occur more quickly
changes in cell movement, secretion, or metabolism
Signaling molecules eventually interact with _, altering them to change the behavior of the cell in various ways.
specific effector proteins
Intracellular signaling proteins can relay, amplify, integrate, distribute, and modulate via _.
feedback an incoming signal
a receptor protein located on the cell surface _ an extracellular signal into an intracellular signal
transduces
Note that some proteins in the pathway may be held in close proximity by a _, which allows them to be activated at a _ in the cell and with greater speed, efficiency, and selectivity
scaffold protein
specific location
a downstream protein in a signaling pathway, protein Y, acts to _ the activity of the protein that activated it—a form of positive feedback.
increase
Positive feedback loops can ignite an _ response, such as the activation of the proteins that trigger cell division
explosive
In a simple example of negative feedback, protein Y _ the protein that activated it.
inhibits
The activity of monomeric
GTPases is controlled by two types of
regulatory proteins. _ promote the
exchange of GDP for GTP, thereby switching the protein on. _ stimulate the hydrolysis of GTP to GDP, thereby switching the protein off.
Guanine nucleotide exchange factors (GEFs)
GTPase-activating proteins (GAPs)
Two messenger molecules are produced when a membrane _ is hydrolyzed by activated _. _ diffuses through the cytosol and triggers the release of _from the ER by binding to and opening special _ channels in the ER membrane. The large electrochemical gradient for _ across this membrane causes _
to rush out of the ER and into the cytosol. _ remains in the plasma membrane and, together with _, helps activate the enzyme _, which is recruited from the cytosol to the cytosolic face of the plasma membrane (Movie 16.4). _ then phosphorylates
its own set of intracellular proteins, further propagating the signal.
inositol phospholipid
phospholipase C
Inositol 1,4,5-trisphosphate (IP3)
Ca2+
Ca2+
Ca2+
Ca2+
Diacylglycerol
Ca2+
protein kinase C (PKC)
PKC
