Ligand Binding Receptors Regulating Transcription Flashcards
What happens when estradiol binds to its receptor?
Causes a conformational change in the receptor that enables it to associate with coactivator proteins and bind to regulatory DNA sequences of target genes.
Which genes are regulated by estradiol?
Approximately 1000 genes involved in cell growth and division.
What is TGFb signaling?
A pathway that regulates transcription through the SMAD2/3-SMAD4 complex activating transcription of target genes in the nucleus.
What is the role of phosphorylated SMAD2 or SMAD3 in TGFb signaling?
They dissociate from the receptor and bind to SMAD4.
True or False: TGFb receptors have enzymatic activity.
False. The receptor does not have enzymatic activity but activates a kinase that initiates a signaling pathway.
What happens when extracellular dimeric TGFb ligand binds to a Type II receptor?
It causes the Type II receptor to bind to and phosphorylate a Type I receptor, activating it.
What is the structure of the TGFb receptor?
It is a transmembrane protein with serine/threonine kinase activity and consists of Type I and Type II receptors.
How is the active TGFb ligand produced?
By the proteolytic cleavage of the propeptide outside the cell.
What is the primary function of TGFb?
Regulates growth, cell division, immunosuppression, cell differentiation, and dorso-ventral specification.
How many TGFb isoforms do humans have?
Three.
What is the role of erythropoietin (EPO) in JAK/STAT signaling?
Stimulates erythrocyte production in bone marrow in response to hypoxia.
What occurs when EPO binds to its receptor?
The receptor dimerizes and activates JAK, which phosphorylates tyrosine amino acids on the receptor.
What do STAT transcription factors do in JAK/STAT signaling?
They bind to phospho-tyrosines on the receptor and are phosphorylated by JAK kinase.
Fill in the blank: The receptor for estradiol is the _______.
estrogen receptor (ER).
What effect does tamoxifen have on estrogen receptors?
It competes with estradiol for binding, causing an allosteric change that results in a non-functional ER.
What percentage of breast tumors have increased levels of estrogen receptors?
60-70%.
What is the role of coactivators in estrogen signaling?
They are required for the transcription of genes regulated by estrogen receptors.
What initiates signaling between adjacent cells?
Direct physical interaction via surface components.
What is the primary function of the estrogen receptor (ER)?
To bind estradiol in the cytosol, form a dimer, and translocate to the nucleus to regulate transcription.
What is the source of estradiol in the body?
Mainly produced in the follicles of the ovaries, but also in other tissues.
True or False: Estradiol is a lipid-soluble molecule.
True.
What is the first step in the synthesis of TGFb?
Synthesis with a signal peptide that targets it to the endoplasmic reticulum.
