Cell signaling pathways and consequences in the cell

Question 1

Contact dependent signaling

Answer 1

Signals are transmitted by direct contact of signal molecules and receptor proteins which are bound to/lodged in the membrane of the interacting cells.

Question 2

Synaptic/neuronal signaling

Answer 2

Neurons excrete neurotransmitters which diffuse over the synapse and affect the target cells. Local, specific signaling.

Question 3

Paracrine signaling

Answer 3

Signaling molecules are secreted locally and act on nearby cells (e.g. signal molecules that regulate inflammation). Distance bigger than a synapse but limited to certain tissues/distances.

Question 4

Endocrine/hormonal signaling

Answer 4

Signaling molecules (hormones) are secreted into the bloodstream and travel through the body until they find the right receptor.

Question 5

Does the same receptor always mean that the cell responds in the same way?

Answer 5

No, a different cell can have a different reaction to the activation of the same receptor. The same receptor and signaling molecule can also have a different effect when the concentration differ.

Question 6

Can one cell recieve different signals at once?

Answer 6

Yes, this happens in almost every cell. For example it is very common that a cell always recieves a ‘stay alive’ signal, while also recieving signals to grow and divide of to differentiate.

Question 7

Positive feedback

Answer 7

The output signal molecule stimulates its own production.

Question 8

Negative feedback

Answer 8

The output signal molecule inhibits its own production.

Question 9

Intracellular signaling pathways

Answer 9

A cascade of activations which will lead to a cellular response.

Question 10

The two types of extracellular signaling molecules

Answer 10

Lipophilic and hydrophilic

Question 11

Lipophilic signaling molecules

Answer 11

Small and hydrophobic, these signaling molucules can move over/go through the cell membrane and therefore can bind to intracellular receptors.

Question 12

Intracellular receptors

Answer 12

Receptors that are in the cell, most often on the nuclear membrane.

Question 13

Hydrophilic signaling molecules

Answer 13

Large and polar. These signaling molecules bing to cell-surface receptors.

Question 14

Intracelular signal proteins

Answer 14

These proteins can act as molecular switches, because they can exist in an active or inactive conformation. There are two molecular mechanisms that can switch the proteins on and off: Phosphorylation and binding of GTP or GDP.

Question 15

Phosphorylation

Answer 15

When a phosphate group is bound to the protein, this causes the protein to have an extra negative charge, this causes a conformational change and by that the activity or inactivity of the protein.

Question 16

Kinases

Answer 16

Kinases phosphorylates(adds a phosphate to) a protein, turning it on.

Question 17

Phosphatases

Answer 17

Phosphatases dephosphorylates(removes a phosphate from) a protein, turing it off.

Question 18

Binding of GTP or GDP

Answer 18

When GTP is bound the protein has an active conformation(on), when GDP is bound the protein has an inactive configuration(off). The turning on and off happens by binding a GTP or hydrolysing a GTP to a GDP.

Question 19

Guanine exchange factor(GEF)

Answer 19

Swaps out a GDP for a GTP.

Question 20

GTPase accelerating protein(GAP)

Answer 20

Stimulates the GTPase activity.

Question 21

GTPase

Answer 21

GTPase hydrolyses GTP to GDP + Pi.

Question 22

Cell-surface receptors

Answer 22

Cell-surface receptor are transmembrane proteins that can receive a signal form outside the cell and pass the signal by production of for example second messagers. There are 3 types of cell-surface receptors.

Question 23

Ion channel coupled receptors

Answer 23

Signaling molecule binds to the receptor -> there is a conformational change -> Ions can pass the cell membrane. This type of receptor can be found in the nervous system a lot.

Question 24

G-protein coupled receptors(GPCRs)

Answer 24

A CPCR is a polypeptide chain with 7 helices through the cell membrane and has a binding pocket for an intracellular G-protein. The signaling molecule(ligend) binds to the receptor -> the receptor undergoes a conformational change -> activation(GTP binding) of G-protein ->activation of α subunit and β,γ subunit -> regulation of target proteins.
The G-protein is deactivated when the alpha unit hydrolyses its own GTP and the subunits form the inactive G-protein again.

Question 25

G-protein

Answer 25

A trimeric protein that consists of subunits α,β and γ. It is activated when a GTP is added to the alpha subunit and is deactivated when the GTP hydrolyses and the three subunits reunite to form the inactive protein.

Question 26

Enzyme coupled receptors (ECRs)

Answer 26

ECRs are transmembrane receptors that have intrinsic enzymatic activity(kinase activity) after the ligand binds on the outside. There are two types of this receptor.

Question 27

Receptor tyrosine kinase (RTK)

Answer 27

A type of ECR. This receptor consists of 2 domeins. A ligand brings the two domains together -> a first phosphorilation activates the kinase domains -> a second phosphorylation generates binding sites for signaling proteins(often aided by adaptor proteins)(tyrosine are phosphorylate due to the -OH group).

Question 28

Grb2

Answer 28

Grb2 is an adaptor protein that can bind to a phosphorylated RTK with its SH2 domain and to Ras-GEF with its SH3 domain.

Question 29

Ras

Answer 29

A monomeric G-protain that is bound to the membrane. An activated Ras activates the MAP kinase pathway.

Question 30

Ras-GEF(Sos)

Answer 30

A GEF that swaps out GDP for GTP in the Ras protein.

Question 31

The Ras pathway

Answer 31

Grb2(GAP) binds to the ahosphorylated tyrosine receptor and to the Ras-GEF -> Ras-GEF actiates Ras -> Ras (for example) activates the MAP kinase pathway.

Question 32

MAP-kinase pathway

Answer 32

Ras activates Raf (MAP kinase kinase kinase) by binding -> Raf phosphorylates and so activates Mek (MAP kinase kinase) -> Mek phosphorylates and so activates Erk (MAP kinase) -> Erk can phosphorylate gene regulating proteins or change protein activity.

Question 33

RTKs and GPCRs

Answer 33

These receptors can have overlapping signaling pathways.

Question 34

Tyrosine kinase associated receptor

Answer 34

A type of enzyme coupled receptor. When the ligand binds the receptor is activated because a dimer is formed. This activated receptor recruites and activates a cytoplasmic throsine kinase. This can for example activate the JAK-STAT signal pahtway.

Question 35

JAK-STAT signal pathway

Answer 35

JAKs phosphorylate each other to fully activate, create a binding site for the SH2 domain of STAT-proteins and then phosphorylate these STATs. The STATs form a dimer and move into the nucleus to control gene expression.