Cell signaling

cell and molec

chemical signals into electrical ones

ion channel coupled receptors convert

signal transduction

when receptors on target cells receive an incoming extracellular signal and converts it to the intracellular signaling molecules that alter cell behavior

receptors

target cells that possess proteins that recognize and respond specifically to a signal molecule

extracellular signal molecules

proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, dissolved gases

extracellular signal molecules

bind either cell-surface receptors or to intracellular receptors

endocrine signaling

signals that are released into the bloodstream and disperse a signal throughout the whole body

endocrine cells

cells that produce hormones

pancreas

endocrine glands that produce insulin

paracrine signaling

does not enter bloodstream and diffuses locally through extracellular fluid remaining in the neighborhood of the cell that secretes them

paracrine signals

what are considered the local mediators on nearby cells?

paracrine signaling

inflammation at the site of infection has many signals that control wound healing

autocrine signaling

cells that respond to their own signal and are a form of paracrine signaling

autocrine signaling

cancer cells promote their own survival and proliferation through

neuronal signaling

can deliver messages over long distances, but not widespread

neuronal signaling

axon and electrical impulses will send signals that convert into chemical form. This is an example of

neurotransmitter

Neuronal signaling stimulates a nerve terminal to release an extracellular signal called a

target cell

The neurotransmitter diffuses across to the axon terminal on the

contact-dependent signaling

most intimate and does not require the release of a secreted molecule

contact-dependent signaling

occurs through the physical contact of proteins embedded in the plasma membrane

contact-dependent signaling

occurs in development when adjacent cells are initially all similar to each other, these cells communicate to become specialized into different cell types

contact-dependent signaling

What type of signaling is important for the immune system and survival of many cells?

endocrine glands

hormones produced in ___________ are secreted into the bloodstream and are distributed widely throughout the body

paracrine signals

are released by cells into the extracellular fluid in their neighborhood and act locally

neuronal signals

are transmitted electrically along a nerve cell axon. when this electrical signal reaches the nerve terminal, it causes the release of a neurotransmitter onto adjacent target cells

contact-dependent signaling

a cell-surface bound signal molecule that binds to a receptor protein on an adjacent cell

receptor

whether a cell responds depends on whether it possesses the correct

signal

Each receptor is activated by only one type of

signal

Without the receptor, the cell won’t be able to receive the

effector proteins

molecules that are affected by signal transduction

interprets

the information conveyed by the signal depends on how the target cell receives and _________ the signal

effector proteins

response time can vary, some can be fast others slow

target cells

the same signal molecule can induce different responses in different

survive

an animal cell depends on multiple extracellular signals to

intracellular enzymes/ receptors

extracellular signals being either cell surface receptors or

1\. large hydrophilic

2\. small hydrophobic

There are two classes of extracellular signals

die

if you don’t get extracellular signals, you

steroid hormones

cortisol, estradiol, testosterone and thyroid hormone are all examples of

steroid hormones

hydrophobic molecules that pass through the plasma membrane and bind to receptors in the cytosol or nucleus

nuclear receptors

the name for both cytosolic and nuclear receptors

nuclear receptor

each hormone binds to a different

DNA

each receptor acts at a different set of regulatory sites on

intracellular signaling (large hydrophilic)

transmembrane receptor that detects a signal on the outside and relays the message across the membrane into the interior of the cell

intracellular signaling

works like a molecule relay race where the message is passed down from one intracellular molecule to another

relay

____________ the signal outward, help spread it through a cell

amplify

___________ the signal received, so it will make it stronger so that a few extracellular signals promote a large intracellular response

integrate

signals from more than one intracellular signaling pathway that are integrated before they move onward

distribute

signal can be passed to more than one effector protein

Feedback regulation

signaling pathways can be subject to this modulation

positive feedback loop

a downstream component that acts positively on an earlier component, thus enhancing the signal

negative feedback loop

downstream component that acts to inhibit an earlier component, diminish the response of the initial signal

trimer and the monomer

What are the two types of G-proteins?

G-protein trimer

has three subunits and its own GTPase activity

G-protein monomer

requires help from other proteins for GTPase activity

active

remain in active state until they receive a signal and become

protein kinase

phosphate groups being covalently attached to proteins

phosphatase

phosphate group is removed

phosphorylation cascades

molecular switch proteins are often protein kinases that cascade and activate other protein kinases

serine/ threonine kinases

phosphorylate proteins on ser/thr

tyrosine kinase

phosphorylate proteins on tyr

1\. serine/threonine kinase

2\. tyrosine kinase

3\. GTPase activity

what are the three types of molecular switches?

GTP binding proteins

toggle between active and inactive state depending on whether they have GTP or GDP bound proteins

GTPase activity

when GTP-bound proteins are hydrolyzed into GDP, the proteins become inactive or shut off

GTP

active when bound to

GDP

Inactive when bound to

exchange of GDP for GTP, switching the protein on

Guanine nucleotide exchange factors (GEF)

GTPase-activating proteins (GAPS)

hydrolysis of GTP to GDP, the protein will be switched off

ion-channel coupled receptors

changes permeability of plasma membrane to selected ions, therefore altering the membrane potential

ion channel coupled receptors

responsible for the rapid transmission of signals across synapses in the nerve system

electrical signal

Ion channel coupled receptors transduce a chemical signal in the form of secreting a neurotransmitter, which is delivered to the outside of the target cell and is converted directly into an

opens an ion channel in the PM

When a neurotransmitter binds to a receptor, it ___________, which allows for the flow of a particular ion

an electrochemical gradient

What is the movement of ions driven by?

ion channel coupled receptors

these function most in stimulated cells like neurons and muscles

G-protein coupled receptors (GPCRs)

cell surface receptors that can respond to hormones, local mediators, and neurotransmitters

G protein coupled receptors

attractive drug target

7 times

a single polypeptide chain passes through the PM

seven

____-pass transmembrane protein

G-protein coupled receptors

activate or inactivate an enzyme or ion channel in the plasma membrane and initiates a signaling cascade

trimeric G proteins

composed of alpha, beta and gamma subunits

lipid tail (hydrophobic)

Each subunit of trimeric G proteins are tethered to the PM by the

alpha bound to GDP

inactive state of a trimeric G protein

activates a G-protein

extracellular signal binds to the G protein coupled receptor, which causes a conformational change in the receptor that _________, which is on the other side of the PM

alpha

when activated, alpha exchanges GDP for GTP, and then ______ detaches from beta/gamma subunit, which are now also activated

target proteins

Now that the alpha subunit and the beta/gamma subunits are activated, they can all interact with ______ and relay signals to other destinations in the cell

signaling you’re going to get

The longer the target proteins remain bound to the alpha and beta/gamma subunits, the more

alpha

______ determines the length of the target proteins

hydrolyzed

when GTP is ________ on alpha, the G-protein will return to its inactivate state

seconds

GTP hydrolysis and inactivation occurs within

adenylyl cyclase

produces cyclic AMP and activates cyclic AMP dependent protein kinase (PKA)

phosphorylate

binding of cyclic AMP (cAMP) and PKA can now __________ targets and will have varying functions based on the cell

adrenaline

binds a class of GPCRs that produces cyclic AMP

glycogen

for skeletal muscle, ______ is broken down for maximizing the amount of glucose that is available as fuel for muscular activity.

activates gene transcription

rise in intracellular cyclic AMP (cAMP),

adenylyl cyclase

GPCR activates

adenylyl cyclase

activates cyclic AMP, which activates PKA, PKA moves into the nucleus and PKA phosphorylates specific transcription factor to allow for transcription

adaptor protein

_________ docks on the phospho-tyrosine of the activated receptors, the adaptor then recruits a Ras guanine nucleotide exchange factor (Ras-GEF) that stimulates Ras to exchange its bound GDP for GTP, the Ras protein is now activated, so that it can stimulate several downstream signaling pathways

active

signaling molecules bind to the receptor, the receptor dimerizes and triggers the phosphorylation of tyrosine-domains. adaptor proteins then bind and interact with G-protein, Ras. Ras then becomes _____ by binding GTP. Phosphorylate next substrate now because it starts a downstream signaling pathway.

MAP kinase

Ras activates a ________ signaling molecule.

MAP kinase

Ras protein is activated and it will then activate a three-kinase signaling molecule which relays a signal downstream. ________, which is the final module then phosphorylates various downstream signaling or effect proteins

GEF and GAP

Ras needs

intracellular signaling pathways

Both GPCRs and RTKs (receptor tyrosine kinase) activate multiple