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study notes for lecture four: receptors and signalling

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Department
Physiology
Course Code
PSL201Y1
Professor
Doug Mac Kay

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LECTURE FOUR: RECEPTORS AND SIGNALLING
Q: how do sex steroids interact with their receptors to give male or female characteristics?
4KRZGRHVHSLQHSKULQHVLJQDO³ILJKW-or-IOLJKW´UHVSRQVHXVLQJ*-proteins?
Q: how can insulin activating its tyrosine kinase receptor still result in diabetes?
\ÆA: disease affects the cascade
LQVXOLQFDQVWLOOELQGWRWKHUHFHSWRULW¶VWKHFDVFDGHWKDWLVDIIHFWHG^WKHFDVFDGHWKDWUHVXOWVIURPWKHELQGLQJRILQVulin})
HORMONAL SIGNALLING
Mechanism
Effects
Other Considerations
- hormone binds to complementary site on
receptor in nucleus or cytoplasm
- XSRQELQGLQJWRUHFHSWRUWKHUHFHSWRU¶V
conformation and activity change
- LQWUDFHOOXODUVLJQDOOLQJSDWK¶VDFWLYLW\FKDQJHV
target cell responds
o will not affect receptors that are not of
interest
o target cells are cells that express the
appropriate receptors for the hormones
of interest
lipophilic hormones
Ætestosterone (an androgen) Æestradiaol (an estrogen)
\Æmales and females Æonly in females {ovaries}
((why does a hormone bind its own receptor?))
Æhigh affinity
ÆVDWXUDEOH UHDFKDSODWHDXWKHPRUHKRUPRQH\RXDGGZRQ¶WDIIHFWWKHELQGLQJUDWHRQFHWKHSODWHDXKDVEHHQUHDFKHGRQO\Vo many receptors)
Æspecific = because of the complimentary sequences oIOLJDQGVDQGUHFHSWRUVQHHGVWREHVSHFLILFRUHOVHWKHKRUPRQHZRQ¶WNQRZZKHUHWRDFW
Æreversible = binding of hormone to a receptor is not permanent, there are multiple ways of regulating binding
Q: if you add more hormone, will more hormone bind its receptor?
A: Æyes, it will ± increases in a linear fashion, until it reaches a plateau where all the receptors have been bound by hormones = saturated
::X-axis = total labelled testosterone (nM) ::Y-axis = bound labelled testosterone (fmoles/mg protein)
Q: can you remove hormone from its receptor?
A: Æassign an arbitrary number for the amount of bound labelled hormones ± assume 100%
Æadd non-labelled hormone and the more non-labelled hormone added, the more the amount of bound labelled hormones declines
\Æthis is because the new non-labelled hormone added is competing with the labelled hormones for binding sites on the receptor
::X-axis = non-labelled steroid concentration (M) ::Y-axis = labelled steroid bound
www.notesolution.com
((what characteristics do receptors share?))
Ælarge proteins
Æfamilies (receptors are organized into families based on their
functional properties)
Æmultiple receptors for one ligand (can have opposing functions ±
depends on the target tissue) *note: possible because it is the receptor
that determines the function of the hormone
Ævariable number in target receptors/cells
Æactivated and inhibited
Ælocated in cell membrane, cytoplasm, nucleus
(depends on types of hormones that bind to it)
SPOTLIGHT ON:ESTROGEN
Composition
Mechanism
Effects
Other Considerations
- formed from testosterone
- formed in the ovaries
because the ovaries contain
aromatase ± a converting
enzyme
enters the cell and bind to its receptor in the
cytoplasm
estrogen response element in DNA ± sequence that
can interact with estrogen and estrogen-formed
complexes
estrogen response element allows binding of
estrogen+its receptor to DNA
estrogen complex moves into the nucleus and with
co-activator, binds to DNA
DNA-hormone-co-activator complex binds to the
particular DNA fragment that is responsible for
synthesis of female proteins
o only turns on a
particular fragment of
DNA/certain genes ±
genes that give female
characteristics
¾ having a receptor inside
the cell and having
subsequent movement into
the nucleus can have direct
effects on gene expression
¾ the binding of estrogen to
DNA is the rate-
limiting/control step
¾ co-activator is a very
important mediator
4KRZGRSHSWLGHDQGDPLGHKRUPRQHVZKLFKFDWGLIIXVHWKURXJKWhe lipid membrane change intracellular activity?
Æhormone binds onto receptors outside of the cell
*receptors are (I) receptor-enzymes = linked to kinases, or (II)-protein-coupled receptors = epinephrine or glucagon
Æinside the cell there is a second messenger system that is activated by extracellular hormone binding
Æthis results in the phosphorylation of proteins
Æleads to cellular response
www.notesolution.com

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Description
LECTURE FOUR: RECEPTORS AND SIGNALLING Q: how do sex steroids interact with their receptors to give male or female characteristics? K4Z40805L305K7L308LJ3,O1LJK9-or-1OLJK970854380:8L3J*-proteins? Q: how can insulin activating its tyrosine kinase receptor still result in diabetes? A: disease affects the cascade L38:OL3.,389LOO-L3949K070.05947L989K0.,8.,09K,9L8,110.90^9K0.,8.,09K,9708:O9817429K0-L3L3J41L38ulin}) HORMONAL SIGNALLING Mechanism Effects Other Considerations - hormone binds to complementary site on target cell responds o will not affect receptors that are not of receptor in nucleus or cytoplasm interest - :543-L3L3J9470.059479K070.059478 o target cells are cells that express the conformation and activity change appropriate receptors for the hormones - L397,.0OO:O,78LJ3,OOL3J5,9K8,.9L;L9.K,3J08 of interest lipophilic hormones testosterone (an androgen) estradiaol (an estrogen) males and females only in females {ovaries} ((why does a hormone bind its own receptor?)) high affinity 8,9:7,-O070,.K,5O,90,:9K02470K4724304:,Z439,110.99K0-L3L3J7,9043.09K05O,90,:K,8-00370,.K0 43O8o many receptors) specific = because of the complimentary sequences o1OLJ,38,370.059478300894-0850.L1L.470O809K0K472430Z439N34ZZK07094,.9 reversible = binding of hormone to a receptor is not permanent, there are multiple ways of regulating binding Q: if you add more hormone, will more hormone bind its receptor? A: yes, it will increases in a linear fashion, until it reaches a plateau where all the receptors have been bound by hormones = saturated ::X-axis = total labelled testosterone (nM) ::Y-axis = bound labelled testosterone (fmolesmg protein) Q: can you remove hormone from its receptor? A: assign an arbitrary number for the amount of bound labelled hormones assume 100% add non-labelled hormone and the more non-labelled hormone added, the more the amount of bound labelled hormones declines this is because the new non-labelled hormone added is competing with the labelled hormones for binding sites on the receptor ::X-axis = non-labelled steroid concentration (M) ::Y-axis = labelled steroid bound www.notesolution.com
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