Exam 1 Flashcards
Difference between each cell in an organism
Expression of genes, which determines proteins in the cell
Signal Transduction
Cell communication. Ligand binds to a receptor to cause a change within a cell.
A ligand acts as
signal
2 main changes, fast and slow options
Can impact Txn or Tln, making changes in proteins produced and their rates, very slow(mins to hrs). OR modulates protein function(ms to mins)
Possible cell behavior changes as a result of the signals
Cell division, cell differentiation, cell death/apoptosis, cell survival, and others
Phosphorylation and GTP binding
Adding a phosphate group. GTP can bind to enzymes to turn proteins on or off.
4 Signaling modes
Juxtacrine, paracrine, autocrine, endocrine
Juxtacrine signaling
Cell touches an adjacent cell to send it a signal, no release of ligand required. Examples are Caherin and Integrin.
Paracrine signaling
medium range signaling. ligand is released 1-20 cell diameters away where it is received by receptor cell. often used by nerve cells with neurotransmitters.
Signals that cross the PM
bind to intracellular receptors. examples are steroids (4 C rings hydrophobic lipids that can pass through the PM, hormones like testyosterone, estradiol, cortisol, vitamin D, retinoic acid. uses endocrine signaling. receptor protein in cytoplasm is Txn factor that carries the signal to the nucleus to change transcription of proteins(slow)) Other example is nitric oxide, usually with paracrine signaling due to instability of the gas. Binds to protein Guanylyl Cyclase, which takes 2PO4 groups from GTP to make cGMP, which is then used for muscle relaxation and blood vessel dilation(fast).
Autocrine signaling
self-signaling. cell releases a ligand that binds to itself, causing a positive feedback loop. an example is when T lymphocytes release cytokine to rebind to the cell and cause it to divide repeatedly to create more lymphocytes.
Endocrine signaling
long ranged signal. signaling cell sends ligand through blood and lymphatic system to receiving cell, which is far away. Examples include hormones from thyroid, parathyroid, adrenal, pancreas, gonads. ONLY works if there is a circulatory and lympathic system.
2 categories for the ligand’s binding location.
Signals that cross the PM, and signals that bind to receptors and proteins IN the PM.
Eicosanoids
example prostaglandins, signals result in proliferation and inflammation, impact blood flow with vasoconstriction and vasodilation. autocrine and paracrine signaling. uses receptors with associated enzymes.
Examples of Signals that bind to the receptors and proteins in PM
Neurotransmitters are small, hydrophilic so cannot cross PM. Sent as signals from nervous system. Binds to LGICs, or GCPRs. Proteins and peptides are also hydrophilic and range in size so they can’t cross PM. Include growth factors (epithelial, nerve, vascular endothelial, platelet), and peptide hormones like insulin. Cytokine signals used in lymph cells for autocrine signaling. Use GCPRS or receptor tyrosine kinase(can also be receptor with associated enzyme)
Ligand gated ion channels (LGICs)
Internal membrane proteins that serve as receptors. binds to ligand, which opens the gate. Hydrophobic outer coat with hydrophilic inner coat. often Hphobic alpha helix(structure in secondary proteins). Polarity is a result of amino acid R-group being a hydrocarbon. Gate allows ion flow while open, stops flow while closed (facilitated diffusion).
G-protein coupled receptors (GPCRs)
Membrane protein whose N-terminal end has a receiving cup on the outer side of cell and is coiled through the PM 7 times (7 pass transmembrane protein). Inner section C-terminal is intracellular domain, outer is extracellular. Hphobic alpha helix. Receptor coupled to heterotrimeric (3 subunits alpha beta gamma) g protein. Circular structure, leftmost alpha, rightmost beta. Crescent shape attached to ab, which is the gamma portion. Signal usually NT or growth factor
Pathway of signals in GPCRs
Signal received on outside causes inner change. Ligand binds to N-terminal cup, causing change in confirmation in receptor. Alpha subunit kicks off GDP and replaces it with GTP using a guanine exchange factor GEP. Then, A activates, dissociating from BG(which is now activated as well). When deactivated by removing ligand, GAP Guanine Activating Protein activates an enzyme that removes a phosphate group, returning Alpha to GDP resting state.
Receptors with Intrinsic enzyme activity
Example is tyrosine kinase, protein that serves as a receptor and enzyme. Kinase, the enzyme, phosphorylates proteins. Tyrosine is an amino acid that is able to be phosphorylated. Serine and threoine are other examples of kinases which control cell death, proliferation, etc.
Pathway and Structure of Receptor w/ intrinsic enzyme activity
Extra-cellular domain and intracellular domain. Two N terminal receptors receive a ligand dimer(2 ligand), which pulls them together in a bond. The dimerization causes autophosphorylation in the kinase portion of the enzyme, which allows the C terminal ends to phosphorylate each other across the ICD. The now-phosphorylated tyrosine is used as a binding site for signaling proteins to continue the signal.
Pathway and Structure of receptor with associated enzyme activity
Example Cytokine receptor. Enzyme is attached to the receptor portion. Similar activation as IEA, but the associated enzyme has to bind to the activated receptor to phosphorylate.
Cyclic AMP pathway
Example GPCR. Ligand binds, causing the receptor to conform to cause a GEF in alpha. Once alpha gains GTP, it activates and pushes BG away. (neurotransmitters ex) Alpha activates Adenylyl cyclase, which in turn removes 2 phosphate groups from ATP to make cAMP. cAMP then binds to Protein Kinase A’s 2 R sites, causing them to activate and split off from their Catalytic sites. The Catalytic sites either go into the nucleus and phosphorylate txn factor CREB to change expression of proteins. Other site goes directly to cytoplasmic glycogen synthase to inhibit glycogen synthesis.
MAPK pathway
RasRafMekErk. Examples platelet derived growth factor or vascular endothelial GF with RTK. Ligand bind, dimerization, autophosphorylation. GEF binds to tyrosine with SH2 domain to grab phosphorylated residue. GEF then binds to RasGDP, monomericGprotein, which replaces its GDP with GTP. RasGTP then activates protein Raf, which then phosphorylates Mek, which then phosphorylates Erk. ERK finally can phosphorylate a txn protein in nucleus or other proteins in cytoplasm.
Platelet Derived Growth Factor binding…….
Causes production of cyclin and collagen, making new cells and sticking them together collectively.
Vascular Endothelial GF
causes growth in blood vessels to increase blood flow.
