Signaling Pathways

Question 1

list genes involved in development code for mRNAs

Answer 1

transcription factors
signaling molecules
receptor molecules

Question 2

signal transduction pathways are established when ? and result in ?

Answer 2

when a ligand binds to a receptor

result in a signal being transmitted to the nucleus of responding cell

responding cell produces gene products that influence the developmental pathway of the cell

Question 3

list signaling factor families as discussed in lecture

Answer 3

1. transforming growth factor - beta superfamily
2. fibroblast GF family
3. hedgehog family
4. Wnt family

Question 4

activation of TGF - Beta1

Answer 4

occurs when the proregions are separated from the bioactive dimer

the bioactive dimer then can function as a signaling molecule

Question 5

bone morphogenetic proteins are apart of what GF family?

Answer 5

TGF-b1

Question 6

describe bone morphogenetic proteins

Answer 6

15 members

often inhibit other processes in the embryo

–bind to bioactive dimers to inhibit them

Question 7

fibroblast GF family

Answer 7

22 members

regulation at memb of responding cells and w/ various parts of signal transduction machinery

Question 8

hedgehog family

Answer 8

(related to drosophila)

include:
desert
indian
sonic hedgehog

Question 9

Wnt family

Answer 9

18 members in mouse

related to drosophila

plays dif. roles in various animals but often interacts w/ parts of extracell matrix

Question 10

cell surface receptors have _______ protein _______ activity and ?

Answer 10

intrinsic protein kinase activity

and utilize a 2nd messenger system

Question 11

cell surface receptors include receptors for ?

Answer 11

fibroblast GFs
–tyrosine kinase

TGF-b1
serine/threonine kinase

Question 12

examples of signaling pathways

Answer 12

delta-notch
receptor tyrosine kinase
hedgehog
Wnt signaling
MicroRNA
retinol

Question 13

components of delta-notch pathway

Answer 13

delta = signaling molecule
notch = receptor on neighbor cell

Question 14

activation of delta-notch pathway

Answer 14

delta proteolytic cleavage of notch intracell domain

intracell domain then complexes w/ deltex

complex enter nucleus
–binds to suppressor of hairless

notch-delta-suppressor complex binds enhancer of split

resultant inhibitory signal represses gene expression

Question 15

define lateral inhibition

Answer 15

–type of signaling between a dominant cell and neighboring cells

Question 16

describe what dominant cell means

Answer 16

refers to a cell in a population that begins to differentiate along a particular path

Question 17

process of lateral inhibition

Answer 17

dominant cell expresses delta signaling

delta binds notch on neighbors

represses genes in neighboring cells – to stop neighbors from becoming what the dominant cell is
(ex. neurons)

Question 18

receptor tyrosine kinase pathway can be utilized by ?

Answer 18

fibroblast GF family
and
TGF-b1 family

Question 19

receptor tyrosine kinase – fibroblast GF family components and actions

Answer 19

FGF binds receptor tyrosine kinase

G protein is activated
(RAS, RAF, MAP kinase, ERK)

result = ERK translocates to nucleus and activates various transcription factors

Question 20

receptor tyrosine kinase – TGF - b1 components and actions

Answer 20

TGF-b1 binds serine/threonine kinase receptor type II

receptor type II dimerizes w/ type I

activation of R-Smad and Co-Smad

Question 21

receptor tyrosine kinase — TGF - b1 results

Answer 21

Smad dimer translocates to nucleus and binds to co-factors which can then bind to DNA regulatory factors

Question 22

hedgehog pathway

Answer 22

sonic hedgehog protein
–complexes w/ cholesterol after being translated in sending cell (shh-c)

shh-c translocates to cell surface as product of dispersed gene

Question 23

actions of shh-c

Answer 23

hedgehog pathway

inhibits the inhibitory actions of Patched on smoothened on the target cell

Question 24

results of hedgehog pathway

Answer 24

uninhibited Smoothened signals the release of transcription Gli

from a complex on microtubules

Gli translocates to the nucleus and influences gene expression

Question 25

in the absence of Wnt, _______ are bound to an intracellular ________ complex within the ______ cell

Answer 25

beta-catenins

destruction complex

w/in target cell

Question 26

components of Wnt signaling pathway

Answer 26

Wnt molecule = ligand
–binds Frizzled on target

Frizzled interacts w/ intracell Disheveled

Question 27

results of Wnt signaling

Answer 27

disheveled prevents degradation of b-catenins by destruction complex

b-catenins translocate to nucleus and activate transcription factors

Question 28

define MiRNAs

Answer 28

microRNAs

small RNAs – noncoding RNAs that influence gene expression

2 major groups

Question 29

groups of MiRNAs

Answer 29

1. Piwi - interacting RNAs
   piRNA
2. endogenous small interfering RNAs
   endo-siRNAs

Question 30

piRNAs

Answer 30

act during gametogenesis
–especially spermatogenesis

type of microRNA

Question 31

endo-siRNAs

Answer 31

expressed in somatic tissues thru out development

type of microRNA

Question 32

microRNA pathway – components and actions

Answer 32

refer to figure 4.17

**important to note DICER and Argonaute (AGO) protein

Question 33

describe the microRNA pathway

Answer 33

miRNA precursor – hairpin loop so ds

DICER cleaves to ss

miRNA cannot act on mRNA until AGO binds creating the AGO/mi RNA complex

Question 34

retinol pathway components

Answer 34

retinol = vit A = signal molecule

binds to extracell retinol-binding protein = RBP

retinol-RBP complex binds to memb RBP

retinol is released into cytoplasm and binds CRBP 1

Question 35

retinol pathway actions

Answer 35

after a series of enzymatic transformations

retinoic acid is bound to CRABP1 and translocates to the nucleus

Question 36

retinol pathway results

Answer 36

retinoic acid binds to dimer RXR-RAR

which binds to RARE

which activates transcription