Lecture 1b-cell signaling Flashcards
What is the def of cell signaling
cell communication involvies release of substance (e.g. hormones, ligands) from a cell, dection by target cell and conversion of signal to a biological outcome
What are the 3 steps of cell signaling
- Reception: target cell senses the substance in its exogenous environment/ intercellular signaling-contact dependent or contact independent
- Transduction: conversion of the signal via a cascade of molecular events /intracellular signaling
- Response: specific cellular effect attributed to the signaling molecule/E.g: transcription of genes resulting in protein expression mediating a biological response
What are intracellular consquences of hormone receptor interaction
- hormone gated ion channels can change membrane potential
- A receptor enzyme is activated by an extracellular hormone
- a 2nd messenger generated inside the cell acts as a allosteric regulator of one of more enzymes
- a steroid or steroid-like molecule changes a the level of gene expression evia nuclear hormone receptor proteins
- a receptor recruits a soluble protein kinase from the cytosol to trigger a signaling cascade
What are the modes of intercelluar signaling for reception
Contact dependent: Juxtacrine
Contact independent: endocrine, synaptic, autocrine and paracrine
Contact dependent
juxtacrine
contact independent
- Endocrine: sender cell release hormone to go into blood
- Synaptic: with neurotransmitters off sender neuron, synapse and target cells
- Autocrine: taget receptors on the same cell
- Paracrine: sender cell sends local medaitor to target cells
What is transduction
hormones transduce effects through cellular signaling
Tissues capable of responding to hormones have 2 properties in commone:
- They posses a receptor having very high affinity for hormone
- The receptor is coupled to a process that regulates metabolism of the target cells
What are the secreted molecules
- Hormones: peptide and steroid hormones
- neurotransmitters
- Peptides
- lipids
What are the receptors for secreted molecules
Intracellular receptors
* Steroid hormones
* Estrogens
* Androgen
Cell surface receptors
* Peptide hormones
* Growth factors
Are intracellar receptors hydrophobic or hydrophillic
Hydrophobic
Are cell surface receptors hydrophobic or hydrophillic
hydrophillic
Explain the process of the glucocorticoid receptors and estrogen receptor
Where is the glucocorticoid receptor found?
cytosol then translocates into the nucleus to activate transcription of a gene
Where is the estrogen receptor located?
Nucleus
What are the two types of steroid hormone receptor activities
- Genomic action: slow (minutes)
- Nongenomic action: Rapid (seconds)
What are the major subtypes of estrogen and what is it synthezied from?
- ERalpha and ERbeta
- from cholesterol
What is the difference of the subtype of estrogen?
The A/B region (ligand independent activation function domain) is larger in the ERalpha
ERa and ERb exert differential effects on what?
growth and differentiation in tissues, including bone, colon, uterus, liver, brain, and mammary gland
What is the therapeutic application of estrogen?
Selective estrogen receptor modulators (SERM)
What is SERM
Selective estrogen receptor modulators
* ER ligands (synthetic)
* Exhibit ER aganistic or antagonistic activity depending on the tissue
* Induce structural changes–>affect ability to interact with cofactors–>different effects gene expression
What is the molecular basis of SERM (ongoing research)
- Receptor sub-type specificity (ERa and ERb)
- Cell type specific co-activators and regulators
- Cell type specific targets
What is tamoxifen
competitive inhibitor of estrogen receptor (aka: SERM)
More facts you need to know about SERM
- ER subtypes are diffrentially expressed in target tissues and can be heterogeneously expressed in a particular tissue
- SERMs have differential affinity for ER subtypes (ERa and ERb)
- SERM binding induces specific conformational changes in ER that inflyence dimerization and binding to varuous co-factors that can determine resultant target gene activation or repression
- 1St STERM used in clinic: Tamoxifen use in ERa positive breat cancer
Explain the picutre of Tamoxifen
In breast tissue, what is the receptor type
antagonist
In uterine tissue, what is the receptor type
agonist: no conformationion change
What does tamoxifen do in breast tissue
- no breast cell proliferation
- decreased cancer risk
