Cell Bio Lecture 2- Cell Signaling Flashcards
what are the 4 major pathways of cell signal entry into the cell?
- hydrophobic channels
- ion channels
- G-coupled protein receptor
- receptor kinase signals
what is cell signaling?
the mechanism in which cells communicate via direct contact or through chemical signals to initiate an outcome
what does cell signaling allow cells to do?
respond quickly to stimuli within the microenvironment to maintain homeostasis
what can dysregulation in cell signaling lead to?
disease
what are the 2 types of cell signals?
- intercellular communication
- intracellular communication
how can intercellular communication occur? (2)
- direct cell contact
- chemical signals traveling short or long distances
define intracellular communication
cells autostimulate themselves
give an example of direct cell contact intercellular communication
juxtacrine signaling like MHC-TCR
give examples of short distance and long distance intercellular communication
short distance: paracrine signaling via epinephrine
long distance: endocrine signaling with FSH, LH
describe how hydrophobic molecules enter the cell
they are hydrophobic so they can diffuse right through the noncharged cell membrane
what kind of molecules commonly utilize ion channels?
second messengers
what is the free diffusion of hydrophobic molecules into the cell also known as?
second messenger system
list 7 examples of known hydrophobic molecules that diffuse through cell membranes
- nitric oxide
- arachidonic acid
- steroids
- O2
- CO2
- N2
- benzene
describe nitric oxide
an important endogenous chemical produced during oxidative stress; has both beneficial and adverse effects and is a hydrophobic molecule that freely diffuses through the cell membrane
describe arachidonic acid
produces many vasodilators and constrictors; important in repro (used to induce labor) and immune responses; is a hydrophobic molecule that freely diffuses through the cell membrane
describe steroids
regulators of transcription via specific receptors and include cholesterol, progesterone, testosterone, and estradiol; all are important hydrophobic molecules that freely diffuse through the cell membrane
describe estrogen as related to cell entry (2)
- also called beta-estradiol; the major female sex hormone in mammals
- an endocrine compound that can bind to estrogen receptors located on the surface of cells or within cells (hydrophobic molecule remember?) and affect cell activity
describe endogenous estrogen
can function as proinflammatory modulator as a means to protect the female against pathogens during the reproductive/early years of life
what is the downside of estrogen?
has been linked to autoimmune diseases and cancer; typically manifested later in life
describe the risk/relation between estrogen and breast cancer; describe prevention
human females and companion animal species who retain their reproductive organs are at an increased risk for mammary/breast cancer; the prevention route in companion species is to spay the animal after 1-3 heat cycles; breeder females are at higher risk for mammary cancer
what are ion channels composed of?
membrane proteins that facilitate the passage of ions through the cell membrane
list 3 ions that commonly use ions channels to enter the cell
- Ca2+
- K+
- Na+
how is the passage of ions through ion channels controlled? what are the two types?
controlled through gates; either
1. voltage-gated channels
or
2. ligand-gated channels
what is the major role of ion transfer?
to regulate membrane potential
give 3 examples of ion channel blockers and their mechanism of action plus clinical relevance
lidocaine, novacaine, and carbocaine are all topical local anesthetics that block neural sensation by blocking sodium channels
why does calcium have a number of important roles in cell function?
a good number of intracellular enzymes require calcium for activation
describe calcium and give extracellular to intracellular ratio
calcium is a universal signal transduction ion/element influencing cell growth and differentiation; calcium outside is 10,000:1 inside cells so ion channels are hella important to get that calcium inside the cell
what is the major site for sequestered intracellular calcium?
the endoplasmic reticulum
how is intracellular calcium regulated?
by binding proteins like calmodulin and ion exchange pathways
what happens regarding calcium upon external or internal cell stimulation?
intercellular calcium levels rise to facilitate cell signaling pathways
what 2 types of cells are super sensitive to changes/fluxes in calcium levels?
muscle and nerve cells
is parturient paresis (milk fever) a disease?
nope; it’s a management issue
what is parturient paresis?
an acute to peracute afebrile flaccid paralysis of mature dairy cows that occurs within 72 hours post parturition
what does afebrile mean?
hypothermic; the heart is racing but blood is not flowing
what is the general clinical presentation of parturient paresis? (3)
altered mentation, generalized paresis, circulatory collapse
describe the 3 stages of parturient paresis
stage 1: hyper-excitable, tremors, ataxia; lasts less than 1 hour
stage 2: sternal recumbency, cold extremities, tachycardia, lasts 1-12 hours
stage 3: loss of consciousness followed by coma followed by death in 1-3 hours
describe treatment of parturient paresis
provide calcium supplementation; route and approach depends on severity
most common is calcium gluconate salt but can also give IV
what do you have to be careful about if treating parturient paresis with IV calcium? why?
give VERY slowly while auscultating the heart because if you give too much calcium too fast, this can induce cardiovascular shock and death is likely to occur
what is the primary function of cell signaling via G protein coupled receptors?
to transduce extracellular stimuli into intracellular signals through interactions with heterotrimeric G proteins
what is the oldest cell receptor we have categorized?
G protein coupled receptors
what are 3 HELLA important stimuli of G protein coupled receptors?
- vision
- taste
- smell
what is an example of G protein coupled receptors?
beta-adrenergic receptors that bind to epinephrine and prostaglandins
what are 3 types of signaling cell surface receptor kinases?
- tyrosine kinase receptors/receptor tyrosine kinases (RTKs)
- serine/threonine kinase receptors
- non-receptor tyrosine kinases
how do protein kinases function?
by adding phosphate groups to proteins (phosphorylation)
describe RTKs
receptor tyrosine kinases are high affinity cell surface receptors with intracellular tyrosine domains that bind an array of polypeptides; they are key regulators of normal cellular processes and play a critical role in the development of many cancers
describe serine/threonine kinase receptors
transmembrane receptors that contain intracellular serine/threonine kinase domains; bind TGF and can activate MAP kinase signaling cascade downstream
describe non-receptor tyrosine kinases
enzymes that transfer a phosphate group from ATP to a tyrosine residue in a protein
how do receptor tyrosine kinases work?
binding to a specific ligand sends a signal to the cytoplasmic tail of the receptor to phosphorylate tyrosine amino acids, leading to downstream signal transduction pathways within the cell
what are 3 kinds of receptor tyrosine kinases?
- EGFR: epidermal growth factor receptors
- PDGFR: platelet-derived growth factor receptors
- VEGFR: vascular endothelial growth factor receptors
what is good about the tyrosine kinase domains of receptor tyrosine kinases?
the tyrosine kinase domains are common to all kinds of RTKs and make a good target for drugs!
what does decreased signaling of the EGFR family result in?
linked to neurodegenerative diseases like MS and Alzheimer’s
what does increased signaling of the EGFR family result in?
linked to solid tumor formation and metastasis
what is palladia?
a tyrosine kinase inhibitor; the first FDA approved drug to treat cancer; works by targeting the tyrosine kinase domains in increased expression EGFR RTKs
how do most RTKs exist? what is the exception?
most are single subunit receptors but some exist as multimeric complexes
what does JAK-STAT signaling pathway stand for?
Janus Kinase-Signal Transducer and Activator of Transcription
describe the JAK-STAT signaling pathway
a non-receptor tyrosine kinase pathway where a ligand (interferon) binds to a receptor which is associated with JAK that then autophosphorylates and binds STAT; STAT is phosphorylated and translocates to the nucleus where it binds specific DNA to initiate gene transcription leading to protein production (cytokines)
what 5 physiological processes do the JAK-STAT non-receptor tyrosine pathway play a major role in?
- hematopoiesis
- immune regulation
- fertility
- lactation
- growth and embyrogenesis
is there just one ligand and one receptor for the JAK-STAT non-receptor tyrosine signaling pathway? why or why not?
no there are literally so so many ligands and receptors for this signaling pathway because it is one of the MAIN signaling pathways of the body
what does dysregulation of the JAK-STAT non-receptor tyrosine pathway result in?
cancer
what are (2) examples of chromosmal translocation mutations of the JAK-STAT pathway leading to cancer
- TEL-JAK2 chromosomal mutation leads to leukemia
- PCMI-JAK2 chromosomal mutation leads to acute myeloid leukemia, chronic myeloid leukemia, or T cell lymphoma
what is an example of point mutations of the JAK-STAT pathway leading to cancer
a point mutation of V617F or K539L leads to polycythemia vera
describe how JAK-STAT signaling is linked to immune-mediated diseases
atopic dermatitis is a chronic inflammatory disease with a TH2 biased response that is regulated by the JAK-STAT pathway
what is apoquel?
fancy name oclacitinib; is a JAK1 and JAK3 inhibitor to treat canine atopic dermatitis
what is cytopoint?
a JAK inhibitor to treat canine atopic dermatitis
what other 3 conditions is research being done on JAK inhibitors to try to treat?
- psoriasis
- vitiligo
- alopecia areata
describe the MAPK signaling pathway
Mitogen Activated Pathway kinase is a downstream pathway activated indirectly by numerous signals like growth factors
what does activation of MAPK signaling pathway result in? (4)
- cellular growth
- cellular differentiation
- inflammation
- apoptosis
what has dysregulation of MAPK signaling been linked to?
a variety of cancers
what does NFkB stand for?
nuclear factor kappa light chain enhancer of activated B cells
describe the NFkB pathway
a key transcriptional regulator that is central to inflammatory signaling through TLRs, IL-1 receptors, and BCR signaling
what is the clinical significance of the NFkB pathway?
it is a major transcription factor associated with the inflammatory response
what blocks activation of the NFkB pathway?
IkB (inhibitor of kappa B)
what is the mechanism of action of corticosteroid therapy? give 2 examples of drugs that do this
designed to block the cleavage of NFkB during a proinflammatory response; examples are dexamethasone and prednisone
what is ubiquitin?
a small regulatory protein found in all eukaryotic cells which directs protein recycling by attaching proteins for destruction; the ubiquitin protein guides the to-be-destroyed protein to the proteasome to degrade and recycle it
what is dysregulation of the NFkB pathway linked to? (2)
- immune-mediated disease
- cancer
what is beginning to be used to treat some cancers?
the ubiquitin-proteasome pathwa
