Lect. 11 - Signaling Pathways

Question 1

how are signal transduction pathways established?

Answer 1

when a ligand (signaling molecule) binds to a receptor

Question 2

result of signal transduction pathway

Answer 2

signal being transmitted to the nucleus of a responding cell - responding cell produces gene products that influence the developmental pathway of a cell

Question 3

Transforming Growth Factor-beta Superfamily (TGF-B1)

Answer 3

disulfide linked dimer; consists of a large proregion and a bioactive region

Question 4

what forms the dimer in TGF-B1

Answer 4

two bioactive regions after being cleaved from the proregion

Question 5

what is the purpose of the proregion in TGF-B1 after begin cleaved?

Answer 5

they complex w/ the bioactive dimer to maintain it in a latent form

Question 6

When does activation occur in TGF-B1?

Answer 6

when the proregions are separated from the bioactive dimer

Question 7

what part of TGF-B1 functions as the signaling molecule?

Answer 7

bioactive dimer

Question 8

bone morphogenic proteins

Answer 8

encompasses 15 members w/i TGF-B1 superfamily

Question 9

what are the modes of action of the bone morphogenic proteins?

Answer 9

inhibit other processes in the embryo, often by being inhibited by other molecules; bind to bioactive dimers and prevent them from binding to receptors

Question 10

Fibroblast Growth Factor Family number of members

Answer 10

22 members;

Question 11

FGF family means of regulation

Answer 11

modification of interaction w/ heparan proteoglycans in receptor complex; regulation at membrane of responding cell via transmembrane proteins; regulation by molecules that complex w/ signal transduction machinery

Question 12

Hedgehog Family

Answer 12

related to the segment polarity molecules in Drosophila; include desert, indian, sonic hedgehog

Question 13

Wnt Family

Answer 13

includes 18 members in the mouse; related to segment polarity genes in drosophila; often interact w/ components of extracellular matrix; different roles in various vertebrate classes

Question 14

cell surface receptors w/ intrinsic protein kinase activity

Answer 14

includes receptors for FGF (cytoplasmic domain possesses tyrosine kinase activity) and TGF-beta factors (cytoplasmic domain possesses serine/threonine kinase activity

Question 15

in the delta-notch pathway, which signal molecule is on the dominant cell?

Answer 15

delta

Question 16

in delta-notch pathways what is on the neighboring cell?

Answer 16

notch receptor

Question 17

Delta-Notch pathway actions

Answer 17

proteolytic cleavage of notch in intracellular domain which then complexes w/ Deltex and enters nucleus; complex binds to suppressor of hairless; notch-deltex-suppressor of hairless complex binds to enhanver of split

Question 18

what is the result signal from the delta notch pathway?

Answer 18

inhibitory signal represses gene expression

Question 19

lateral inhibition

Answer 19

type of signaling b/w a dominant cell and neighboring cells; the dominant cell is the one that begins to differentiate along a particular path and expresses delta signaling on its membrane.

Question 20

what happens in lateral inhibition after delta signaling molecule is expressed on the membrane of the dominant cell?

Answer 20

delta binds notch receptors on neighboring cells and represses genes in them (through delta-notch)

Question 21

receptor tyrosine kinase pathway is used by what kind of signaling molecules?

Answer 21

FGF and TGF-beta

Question 22

receptor tyrosine kinase pathway components and actions w/ FGF

Answer 22

FGF binds receptor tyrosine kinase; G protein activated (activates RAS, RAF, MAP kinase, and ERK); ERK translocates to nucleus and activates various TFs

Question 23

receptor tyrosine kinase pathway components and actions w/ TGF-beta

Answer 23

Tgf-beta bind to serine/threonine kinase receptor type II which dimerizes w/ receptor type I (activates R-Smad and Co-Smad); Smad dimer translocates to nucleus and binds to co-factors which can then bind to regulatory factors

Question 24

Hedgehog pathway

Answer 24

Shh + cholesterol then translocated to cell surface via Dispersed; it inhibited the inhibitory actions of Patched on Smoothened on target cell

Question 25

In the hedgehog pathway, what is the result of getting an uninhibited smoothened?

Answer 25

it signals the release of transcription Gli from a compelx on microtubules and Gli translocates to the nucleus to influence gene expression

Question 26

Wnt signaling pathway

Answer 26

Wnt binds to Frizzled on target cell; frizzled interacts w/ disheveled; disheveled prevents degradation of B-catenins by the destruction complex; b-catenins translocate to nucleus and activate Tfs

Question 27

What is found in the absence of the Wnt?

Answer 27

beta-catenins are bound to an intracellular destruction complex w/i the target cell

Question 28

miRNAs

Answer 28

small noncoding RNAs that influence gene expression

Question 29

what are the two major groups of miRNAs

Answer 29

Piwi-interacting RNAs (piRNAs) and endogenous small interfering RNAs (endo-siRNAs)

Question 30

piwi-interactingRNAs (piRNAs)

Answer 30

act during gametogenesis (esp. spermatogenesis)

Question 31

endo-siRNAs

Answer 31

expressed in somatic tissues throughout development

Question 32

miRNA pathway

Answer 32

double helical precursor w/ hairpin loop is cleaved by Dicer and the formed miRNA is complexed w/ an Argonaute (AGO) protein; complex cleaves target mRNA molecule inactivating it

Question 33

retinol pathway

Answer 33

retinol binds RBP and complex binds to a membrane RBP; retinol is released and binds CRBP-1; RA is bound to CRABP-1 and translocated to nucleus; RA binds dimer RXR-RAR which binds RARE which activates transcription