Cell Bio- Intro.txt
Card Set Information
Cell Bio- Intro.txt
Cell Bio Biochem
Cells exhibit different characteristics (phenotype) due to...
cell-type specific gene expression.
external influences that regulate expression of specific genes, including...
extracellular ligands and cell-cell contact
molecule that binds tightly and specifically to a protein or macromolecule.
cells interact with extracellular environment (ie....) through ______, which are often located....
hormones, growth factors, etc; receptors (proteins); on the plasma membrane
mechanism of cell communication in which ligands (______) are released from one organ and travel a far distance to the target tissue.
example of endocrine system
insulin is synthesized in beta cells of the pancreas and travel through the blood to target tissues
mechanism of cell communication in which ligands are produced and released in close proximity to the target tissue.
example of paracrine system
neuromuscular junction neuron releases neurotransmitter to affect muscle contraction
mechanism of cell communication in which ligand are produced and released, and then affect the cell of origin.
example of autocrine system
growth factors released from tumor cells
only cells that ___________ can respond to the ligand.
express the gene encoding the specific receptor for the ligand
receptors for __(2)__ are localized to the plasma membrane.
peptide ligands and hydrophilic small molecule ligands
receptors for ______ are localized to the cytoplasm and nucleus.
example of a hydrophobic ligand
three types of receptors that activate intracellular signaling mechanisms and elicit a biological response.
receptor tyrosine kinases (RTKs), G protein coupled receptors (GPRs), steroid hormone receptors
example of a receptor tyrosine kinase (RTK)
epidermal growth factor receptor (EGFR)
multi-domain proteins that are localized to the plasma membrane.
receptor tyrosine kinases (RTKs)
the amino terminal region of a receptor protein is the _______.
receptor domain that has kinase enzymatic activity.
the Src domain of a receptor is localized to the _____.
the carboxy terminal region of a receptor is _____.
receptors must: (2)
1. detect the signal at the ligand binding domain.
2. send the signal into the cell to elicit a biological response.
describe normal RTK function.
1. RTK is positioned in the plasma membrane; ligand binds to the extracellular domain, causing a conformational change that promotes RTK dimerization.
2. RTK dimerization activate kinase activity of the TK domain.
3. Activation of the TK domain results in autophosphorylation of the TK domain.
two results of mutations in the gene encoding the RTK protein.
1. mutation results in change in amino acid, altering RTK conformation and causing ligand- independent dimerization. This results in continuous signaling and uncontrolled growth. (CANCER)
2. mutation truncates RTK protein, resulting in loss of extracellular domain. This results in continuous signaling and growth/proliferation. (CANCER)
if the gene encoding RTK is amplified...
it is over-expressed and the excess RTKs cause inadvertent dimer formation and continuous signaling and growth. (CANCER)
G protein coupled receptors are characterized by...
7 membrane spanning transmembrane domains
4 examples of the wide range of ligands that GPRs can respond to.
1. glucagon receptor- glucose metabolism
2. odorant receptors- sense of smell
3. epinephrine receptor- adrenaline
4. rhodopsin- light receptor in rod cells of the eye
describe the structure of GPRs.
serpentine receptors plus a heterotrimic G protein (α, β, γ) bound to GDP.
describe the activity of GPRs.
1. ligand binding causes a conformational change that causes the α subunit to exchange GDP for GTP.
2. the α subunit dissociate, activating downstream signaling cascades.
3. hydrolysis of GTP from α subunit causes it to reassociate with the β,γ subunits.
example of a GPR
visual pigment contained in the outer segments of the rod cells of the retina and involved in vision under low light conditions.
loss of rhodopsin (GPR) function is associated with _____.
_______ associated with similar clinical signs of blindness across breeds.
progressive retinal atrophy (mutation in rhodopsin gene)
the rhodopsin mutation that causes PRA in english mastiffs is a _____ mutation
missense (C --> G transversion) (T4R substitution)
the mutation that causes PRA in english mastiffs is in the ____ domain, which is _____.
amino terminal; extracellular
The mutation that causes PRA in english mastiffs destroys a ______, creating a ______ that can be recognized using a DNA-based test.
restriction site; restriction fragment length polymorphism (RFLP).
inheritance of the rhodopsin mutation that causes PRA in english mastiffs is _____.
a variation or difference in a DNA sequence from the normal sequence.
a variation in the length of a DNA sequence that is digested with a restriction enzyme; caused by differences in the specific DNA consensus sequence that the restriction enzyme recognizes and digests.
restriction fragment length polymorphism (RFLP)
an alteration in a single nucleotide in which a purine is substituted for another purine, or pyrimidine for pyrimidine.
an alteration in a single nucleotide in which a pr=urine is substituted for a pyrimidine, or vice versa.
Cancer is a disease of _______.
Alterations in the RTKs are typically associated with ______ and _____.
growth abnormalities and cancer
Alterations in GPRs have been linked to diseases, including... (4)
blindness, growth abnormalities, enhanced cell migration and invasion, and cancer.
Genes that encode protein that promote normal cell growth.
A mutated, hyperactive proto-oncogene.
The conversion of a proto-oncogene to an oncogene is always referred to as a __________.
Genes that encode proteins that inhibit or block the cell cycle.
Tumor suppressor gene
What is it called when a tumor suppressor gene becomes the cause of cancer?
what 2 genetic alterations cause "gain-of-function"?
1. increased expression due to amplification
2. mutations that alter conformation of the protein and cause an increase of function
What are the classic biomarkers for human breast cancer that have been paralleled in veterinary medicine?
ER (estrogen receptor), PR, (progesterone receptor), and HER2 (human ERbR-2 receptor)
The kinase function of the EGFR is activated when ________, causing...
the ligand (EGF) binds the extracellular domain; phosphorylation that is NOT random; it is a signaling cascade.
At OSU, what cytoplasmic protein is being studied and for what is it thought to be involved?
STAT3 (signal transducer and activator of transcription) for its role in the activation in canine osteosarcoma
Group of genes that are homologous in nucleotide sequence and amino acid composition; they perform similar, NOT identical, functions in biology.
What 2 members of the HER gene family are involved in normal activation og human epidermal growth factor receptor 2?
HER2 (no known extracellular ligand) and HER3 (no cytoplasmic kinase activity)
The _______ binds to HER3, causing the activation of _____ of _____.
ligand (HRG); MAPK (mitogen-activated protein kinase); HER2
molecule that activate cell division; growth factor
The HER2:HER3 heterodimer promotes cell proliferation and cell survival through the _______ and ________.
MAPK an PI3K pathways
_________ is a monoclonal antibody to the HER2 juxtamembrane domain and inhibits HER2 function.
________ is a monoclonal antibody directed at the dimerization domain of the extracellular component of HER2 and blocks dimerization.
TKIs, such as ______, block ______ function.
LAP (lapatinib); RTK
Glucocorticoid is a subset or group of ________ that influence ________.
steroid hormones; glucose and protein metabolism (inflammation)
Cortisol is a ______ that is classified as a _____.
steroid hormone; glucocorticoid
In the absence of the ligand, cortisol, the glucocorticoid receptor is bound to ______, a type of _____.
heat-shock proteins; chaperone protein
Cortisol diffuses through the membrane because it is ____.
When cortisol binds to the glucocorticoid receptor, what occurs?
GR is released from the heat-shock proteins and it forms a dimer with another GR; this complex is transported to the nucleus.
In the nucleus, the GR-cortisol dimer complex binds and actives...
transcription of glucocorticoid responsive genes.