HRR: cell signaling

Question 1

Name the main types of cell signaling and briefly describe them

Answer 1

• Autocrine: cell signaling to itself
• Paracrine: cell signaling to a nearby cell
• Endocrine: cell signaling to a far away cell
• Cell to cell: cells signaling to a cell right next to them

Question 2

Specify the main classes of plasma membrane receptors

Answer 2

• Transmembrane: integral membrane proteins
• Intracellular receptors: receptors are found within the cytoplasm. They bind to ligands that either diffuse or are transported into the cytoplasm and move to the nucleus to promote transcription. They function as transcription factors that directly regulate transcription of target genes.

Question 3

G- receptors: structure and example

Answer 3

they have 7 transmembrane receptors and an N terminus containing the ligand binding domain. They’re heterotrimeric (alpha, gamma, beta); cAMP and IP3/DAG

Question 4

receptor tyrosine kinases: structure and example

Answer 4

single-pass transmembrane proteins; intrinsic kinases that phosphorylate on tyrosine. EGF and IR pathway!

Question 5

JAKSTAT receptors: structure and example

Answer 5

do not have an intrinsic kinase and use JAKS instead; utilize tyrosine! STAT

Question 6

receptor serine-threonine kinases: structure and example

Answer 6

use intrinsic kinase and serine/threonine; TGF beta

Question 7

Specify 4 types of Gα subunits, their molecular targets, and the 2nd messengers that
are generated following ligand binding to a GPCR

Answer 7

Gas: stimulates adenylyl cyclase, cAMP
Gai: inhibits adenylyl cyclase, cAMP
Gaq: stimulates phospholipase Cb, IP3 and DAG
Ga(12/13): stimulates cytoskeletal proteins, GDP-GTP exchange

Question 8

describe the activation of PKA

Answer 8

adenylyl cyclase converts ATP to cAMP. 4 cAMP molecules bind to the regulatory subunits of PKA, which then dissociate from the catalytic units. Those units are then active and can go on to phosphorylate and regulate target proteins. subunits of and activates protein kinase.

Question 9

describe the activation of PKC

Answer 9

phospholipase C cleaves a lipid in the membrane called IP2 into IP3 and DAG. DAG stays in the membrane and IP3 migrates to an IP3 sensitive calcium channel, causing calcium to be released into the cell. Calcium will bind to PKC, then PKC travels to the membrane and binds to the DAG in the membrane; it is then activated.

Question 10

7. Describe the EGF pathway

Answer 10

uses a tyrosine kinase receptor; A ligand binds to a domain on the extracellular surface and promotes dimerization. This dimerization and activation of intrinsic or associated kinase. Autophosphorylation then occurs. Adaptor proteins then bind to the dimer and a complex consisting of SH2 protein, GEF, and commonly RAS-GDP assembles. GDP becomes GTP, allowing RAS to bind to RAF. This initiates MAP kinase pathway

Question 11

What are some functions of PKB

Answer 11

Preventing apoptosis and increasing protein synthesis

Question 12

8. Describe the IR pathway

Answer 12

uses a tyrosine kinase receptor; Insulin binds to the alpha subunit, causing a conformational change and cross phosphorylation. IRS1 binds to activated IR and becomes phosphorylated on tyrosine. This provides SH2 domains for other docking proteins and an activated PI3 kinase. It then recruits PH domains. PKB is then phosphorylated and activated by PDK1. PKB then dissociates from the membrane and is activated

Question 13

Describe JAK-STAT receptors and their signaling

Answer 13

A ligand binds to a domain on the extracellular surface and promotes dimerization. This dimerization and activation of JAKs. JAKs then phosphorylate each other and the receptor. These phosphorylated sites serve as SH2 domain binding sites. STATs then bind and become phosphorylated by the receptor. The STATs dissociate, dimerize, and translocate to the nucleus.

Question 14

Describe the TGF-β pathway

Answer 14

Ligand binds to a type II receptor, which then recruits a type I receptor. The type I is phosphorylated on serine by the type II, which activates the intrinsic kinase of type I. SMADs then bind and become phosphorylated. Upon phosphorylation, SMADs dissociate and translocate to the nucleus.

Question 15

Describe some regulations associated with TGF signaling

Answer 15

Stimulation of extracellular matrix synthesis, anti-proliferation, metastatic cancer

Question 16

What is the negative regulator of cAMP?

Answer 16

cAMP phosphodiesterase

Question 17

Describe how G protein receptors work

Answer 17

-In the resting state G alpha subunit is bound to GDP.
-Upon ligand binding the G-protein undergoes a conformational change that results in the release of GDP and the binding of GTP. GDP to GTP exchange causes the α subunit to dissociate from the β and γ subunits
-GTP bound Gα can then bind to target enzymes such as adenylyl cyclase which is then activated to catalyze the reaction of ATP→cAMP.
-When GTP is hydrolyzed to GDP, Gα dissociates from the target protein and is available
to re-associate with the G proteins to reform the resting G-protein coupled receptor

Question 18

What receptor type is targeted by drug companies?

Answer 18

G protein

Question 19

What proteins are calcium regulated?

Answer 19

Cl channels, K channels, PKC, adenylyl cyclase, nitric oxide synthetase

Question 20

Describe the regulator of free calcium

Answer 20

Calmodulin; each calmodulin can bind 4 calcium molecules

Question 21

Describe calmodulin in relation to muscle contraction

Answer 21

Calmodulin binds to calcium and brings it to MLCK. This allows for a conformational change that activates the kinase. The kinase can then activate myosin light kinase and produce contraction

Question 22

Describe a large signaling impact of nitric oxide

Answer 22

activate guanylate cyclase to making cGMP and activate PKG

Question 23

What are the major ways of regulating ion channels? What are their usual organizations?

Answer 23

Ligand gating and volage gating; pentamer, tetramer, or trimer

Question 24

What pathways are commonly associated with cancer?

Answer 24

RAS and IP3