a. Referring to the signalling diagrams above, complete the table below. Consider how cell signalling will proceed in a cell exposed to hormone H with each of the following homozygous mutations. Mutant HK expressed? Cyclin A cell cycle cell survival expressed? progression? compared with wildtype. csRH active ? (# refers to the mutants (yes/no) listed above) (yes/no) (yes/no) (yes/no) (same, more, less) # 2 # 3 #1 + #5

Biochemistry
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Chapter1: Biochemistry: An Evolving Science
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Hormone H regulates these effects via its receptors which are found at both the cell surface (csRH)
and within the cell (içRH). The signalling pathways that become activated in the presence of hormone
H are depicted and described below.
hormone
H.
H
H
extracellular fluid
inactive
GTP
inactive
RAS
Lyn
cell-surface
receptor for H (csR»)
icR
GDP
RAS-GTP
hexose
metabolism
cell survival
H
icR
G, phase
(resting)
Raf
HK
GSK-3P
MEK
M
G2
icR
- hexose kinase
ERK
promoter HRE
CDK1
Cyclin A
nucleus
cyclin A
Fos
A promoter
Created in BioRender.com bio
Signalling via the cell surface receptor
Hormone H mediates its cell cycle stimulatory and pro-survival effects by binding to and
activating the cell surface hormone H receptor (csRH).
The activated CSRH activates Lyn, which activates RAS and ultimately the Raf/MEK/ERK
kinase cascade.
Active ERK:
o phosphorylates and inactivates GSK-3B. Inhibition of GSK-3ß promotes cell survival.
inhibits p27, preventing it from inhibiting cell cycle progression.
activates Fos, a transcription factor which promotes cell cycle progression by triggering
Cyclin A expression.
Transcribed Image Text:Hormone H regulates these effects via its receptors which are found at both the cell surface (csRH) and within the cell (içRH). The signalling pathways that become activated in the presence of hormone H are depicted and described below. hormone H. H H extracellular fluid inactive GTP inactive RAS Lyn cell-surface receptor for H (csR») icR GDP RAS-GTP hexose metabolism cell survival H icR G, phase (resting) Raf HK GSK-3P MEK M G2 icR - hexose kinase ERK promoter HRE CDK1 Cyclin A nucleus cyclin A Fos A promoter Created in BioRender.com bio Signalling via the cell surface receptor Hormone H mediates its cell cycle stimulatory and pro-survival effects by binding to and activating the cell surface hormone H receptor (csRH). The activated CSRH activates Lyn, which activates RAS and ultimately the Raf/MEK/ERK kinase cascade. Active ERK: o phosphorylates and inactivates GSK-3B. Inhibition of GSK-3ß promotes cell survival. inhibits p27, preventing it from inhibiting cell cycle progression. activates Fos, a transcription factor which promotes cell cycle progression by triggering Cyclin A expression.
Signalling via the intracellular receptor
Hormone H also binds to and activates the intracellular hormone H receptor (içRH).
The activated içRH translocates to the nucleus where it acts as a transcription factor binding
to a specific sequence called a hormone H response element (HRE) found within promoters
on the DNA.
İcRH – HRE binding upregulates the transcription of the hexose kinase gene, which is
required for hexose metabolism and ultimately cell survival.
Below is a list of mutations commonly found in different components of the hormone-signaling
pathways.
Mutant #1: The įçRH undergoes a loss-of-function mutation.
Mutant #2: GSK-3B can no longer be phosphorylated.
Mutant #3: ERK is constitutively active.
Mutant #4: Lyn undergoes a gain-of function mutation.
Mutant #5: The cyclin A gene's DNA is highly compacted and inaccessible.
a. Referring to the signalling diagrams above, complete the table below. Consider how cell signalling
will proceed in a cell exposed to hormone H with each of the following homozygous mutations.
Mutant csRH active ?
HK expressed?
cell cycle
cell survival
expressed? progression? compared with
wildtype.
Cyclin A
(# refers
to the
mutants
(yes/no)
(yes/no)
(yes/no)
(yes/no)
(same, more, less)
listed
above)
# 2
# 3
#1 + #5
Transcribed Image Text:Signalling via the intracellular receptor Hormone H also binds to and activates the intracellular hormone H receptor (içRH). The activated içRH translocates to the nucleus where it acts as a transcription factor binding to a specific sequence called a hormone H response element (HRE) found within promoters on the DNA. İcRH – HRE binding upregulates the transcription of the hexose kinase gene, which is required for hexose metabolism and ultimately cell survival. Below is a list of mutations commonly found in different components of the hormone-signaling pathways. Mutant #1: The įçRH undergoes a loss-of-function mutation. Mutant #2: GSK-3B can no longer be phosphorylated. Mutant #3: ERK is constitutively active. Mutant #4: Lyn undergoes a gain-of function mutation. Mutant #5: The cyclin A gene's DNA is highly compacted and inaccessible. a. Referring to the signalling diagrams above, complete the table below. Consider how cell signalling will proceed in a cell exposed to hormone H with each of the following homozygous mutations. Mutant csRH active ? HK expressed? cell cycle cell survival expressed? progression? compared with wildtype. Cyclin A (# refers to the mutants (yes/no) (yes/no) (yes/no) (yes/no) (same, more, less) listed above) # 2 # 3 #1 + #5
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