Studied by 7 peopleTrue or False: Cancer cells make relatively large modification to the control machinery inside cells
False
•Cancer cells make relatively minor modifications to the control machinery inside cells; tweak existing controls
True of False: Single cell can express over 20,000 proteins
True
Are most of the proteins expressed in a cell involved for cell signaling?
yes
Immediate early genes
the genes that have increased expression have the proteins already in theme
When cells are exposed to growth factors after being deprived for a certain amount of time, they express certain genes right away called ______ ; this does not require new protein synthesis
Immediate late genes
Delayed early genes
Protein dependent genes
Immediate early genes
Immediate early genes
True or False: Immediate early genes are dependent on the synthesis of new proteins
False
If cycloheximide, a drug that shuts down protein synthesis is added along with the fresh serum, induction of the immediate early genes proceeds normally – What does this tell us??
the genes that have increased expression, have the proteins in them already
cycloheximide
a drug that shuts down protein synthesis
What’s the difference between immediate and delayed early genes?
-Immediate early genes already have the transcription factors/proteins there and do NOT need to be synthesized
-Delayed early genes need newly synthesized proteins/transcription factors in order to be activated
What type of early genes are seen in the orange box?
Delayed or immediate?
Delayed early genes
new proteins were synthesized in order to activate or express them
What type of early genes are seen in the green box?
Immediate early genes
The cell already had preexisting transcription factors that needed to be activated in order to express the genes
No synthesis of proteins required
T or F: Growth factors only cause cells to grow
False
Growth Factors can induce a variety of cellular changes
What are ways growth factors can affect a cell?
Growth Factors can…
Increase the rate of protein synthesis
Induce motility of cells
Reorganization of the cytoskeleton
Protect cells from activation of apoptotic pathways
All of the following are potential effects of growth factors except
inhibition of apoptotic pathways
induction of cell motility
decrease in the rate of protein synthesis
reorganization of the cytoskeleton to promote changes in cell shape
decrease in the rate of protein synthesis
What cellular change is seen ?
Cytoskeletal changes
On the left, there’s no serum and it localized to the surface
On the right is the affected cell, you can see the adhesions, adhering to the substrate is seen
What happens after transphosphorylation ?
Following transphosphorylation, the growth factor receptor attracts cytoplasmic proteins to specific phosphotyrosines
Why does each RTK attract its own set of downstream signaling parters?
The proteins recognize the sequence of amino acids that are next to the tyrosine
The SH2 domains of proteins bind to_____
phosphorylated tyrosine residues
acetylated lysine
phosphorylated lysine residues
phosphoserine
phosphorylated tyrosine residues
What do the numbers in the picture denote?
what do the letters indicate?
Numbers denote the position of the tyrosine residues in the polypeptide chain
Letters indicate the amino acids next to tyrosine (Y) that are recognized by the proteins listed via the SH2 domain
How do proteins recognize the amino acid sequence next to the tyrosine?
The SH2 Domain
Can also recognize phosphorylation tyrosine
What does SOS do in the pic?
It coverts GDP to GTP which activates Ras
What sequences are seen within the intermolecular links between RTK and Ras?
Receptor→ Grb2 → Sos→Ras Or
Receptor →Shc → Grb2 → Sos → Ras
MAPK
mitogen-activated protein kinase
Erk
extracellular signal-related kinase
Ets transcription factor
Ets transcription factor – stimulates expression of important growth-regulating genes, i.e. Fos, Cyclin D1, p21
What is the middle pathway?
The Ras  → Raf → MAP kinase pathway
What does the Ras → Raf → MAP kinase pathway do?
***Raf pathway is responsible for most of the transforming powers of Ras oncoproteins***
This pathway induces the gene expression of Fos and Jun transcription factors – associate with one another to form AP-1 – AP-1 acts as a transcription factor and is often hyperactivated in cancer cells
this pathway also confers anchorage independence and loss of contact inhibition;
also contributes to changes in cell shape associated with transformation by the ras oncogene
What happens when raf protein kinase is introduced into cells in a mutant oncogenes form?
**When Raf protein kinase is introduced into cells in a mutant, oncogenic form, it can evoke most of the transformation phenotypes induced by the ras oncoprotein; Raf pathway is responsible for most of the transforming powers of Ras oncoproteins.
What’s erk 1/2
transcription factors because they can translocate into the nucleus
Are ras proteins always anchored to membrane?
Yes
Which pathway is involved mostly in suppression of apoptosis?
The PI3 kinase pathway
First one
PTEN
**PTEN = phosphatase that removes the phosphate that was added by PI3K from PIP3 to deactivate this pathway
True or false: PI3K attached phosphates to proteins
False
**PI3K attached phosphates to a lipid not a protein
What happens when activated Ras bonds to PI3K
**When activated Ras binds to PI3K it causes it to be closely associated with the plasma membrane
What happens when AKT/PKB is activated
Akt/PKB activation also influences angiogenesis (The production of new blood vessels) – this is poorly understood
What does the Ral pathway control?
The cytoskeleton
Which pathway controls the cytoskeleton?
Ral pathway
Third one
Filopodia
Filopodia – small fingerlike extensions that the cell uses to explore its environment and form adhesions with the extracellular matrix
Lamellipodia
Lamellipodia – broad ruffles extending from the plasma membrane found on the leading edges of motile cells
What do sec5 and exo84 contribute to in the Ral pathway?
Sec5 and Exo84 contribute to Ras-mediated anchorage independent growth
What type of proteins are cdc42 and rac
Cdc42 and Rac are Rho proteins; GTPases (GTP-GDP bound)
What are rho proteins involved in?
Rho proteins are involved in reconfiguring the structure of the cytoskeleton and the attachment the cell makes with its physical surroundings; control cell shape and motility; in cancer cells -- invasiveness
What pathway is shown?
Jak-STAT pathway
Cytokines
Cytokines = growth factors that stimulate components of the hematopoietic system
What do STATs do
**STATs activate target genes that are important for cell proliferation and cell survival; myc, Cyclin D1 and D3
What’s STAT 3 know for?
STAT3 known to be constitutively active in a number of human cancers including melanomas and breast cancers
Which mutant proteins can transform normal cells into cancer cells?
Mutant STAT 3
Mutant STAT 2
Mutant STAT 1
Jak 1
Tyk 2
mutant STAT3 protein can transform normal cells into cancer cells
Ras is active when it is bound to _______
GDP
GTP
ATP
ADP
GTP
What is the role of mTOR in the PI3K pathway?
Stimulate protein synthesis (cell growth)
All of the following are molecules that bind to receptors that activate Jak-STAT signaling pathways except
EGF
interleukins
interferon
egf
Which signaling pathway is most involved in inhibiting apoptosis?
PI3K
Ral-GEFs
Raf
Jak/STAT
PI3K
In the ras-raf pathway, Ets, Elk-1, and SAP-1 represent
transcription factors that are inhibited by Erk1/2
transcription factors that are activated by Erk1/2
translation initiation factors that are activated by Erk1/2
kinases that phosphorylate other proteins in the cell
transcription factors that are activated by Erk1/2
The expression of delayed early genes
does not require the binding of transcription factors
does not require new protein synthesis
is dependent on the translation of new transcription factors
is dependent on the presence of transcription factors being present inside the cell before it is exposed to growth factors
is dependent on the translation of new transcription factors
Note
Flashcard