Comp Exam-White Flashcards
signal transduction
cell to cell communication
signal transduction pathway interruption example with leptin
knockout of leptin gene → mouse gains weight
leptin is released from fat and signals hypothalamus that you are full
endocrine signaling
long distance signaling
freely diffusible signals
long lasting (long half-life in minutes) → takes time to go through the circulatory system to find a target cell
paracrine signaling
acts locally
affects cells nearby (not as freely diffusible)
short lived sigal
syanptic signaling
acts locally
affects cells nearby (not as freely diffusible)
short lived signal
e.g. neurotransmitters
autocrine signaling:
- cells respond to signal that they themselves release, or release to cells of the ____ type
- cell secretes signal that feeds back and binds to a receptor on its own ____
- e.g. ____ ____ in cancer cells
- same
- surface
- growth factors
direct cell signaling:
- e.g. ____ cells
- ____-presenting cells to ____ cells
- immune
- Ag, T
most ligands or hormones are ____ or ____ and can’t get into a cell
they require ____ mediated signaling
hydrophilic or large
receptor
G-proteins are heterotrimeric proteins composed of 3 subunits:
G-proteins are ____ nucleotide-binding proteins
alpha, beta, gamma
guanine
G-protein signaling
ligand binds → activated receptor binds to G-protein (acts as a GEF) → G-alpha releases GDP and binds GTP and dissociates from G-beta/gamma → G-alpha binds and activates adenylyl cyclase → G-alpha hydrolyzes GTP to GDP, dissociates from adenylyl cyclase and binds back to G-beta/gamme (becoming inactive) → adenylyl cyclase generates cAMP from ATP → cAMP acts as second messenger molecule
cholera and G-protein signaling:
cholera toxin modifies G protein by keeping the G-alpha in the GTP active form indefinitely
pathway is always active
pumps Cl- and water out of cell in intestine and causes severe diarrhea
cAMP targets:
- cAMP activates cAMP-dependent ____ that consists of 4 subunits
- inactive PKA: 2 ____ subunits and 2 ____ subunits
- binding of 2 cAMP molecules to ____ subunits of tetramer results in release of active catalytic subunits
- active catalytic subunits can regulate proteins by addition of ____ group: addition of 2 negative charges can change conformation of protein
- can result in ____ or ____ of enzymatic target proteins
- PKA
- catalytic, regulatory
- regulatory
- phosphate
- activation or inactivation
receptor tyrosine kinases:
- enzymatic domain is in the ____ tail of the integral membrane protein
- are used for response to ____ factors
- ligand binding induces ____ of 2 receptor monomers
- ____ occurs (cross phosphorylation)
- receptor acts as a ____ site to recruit other proteins
- binds to ____ with ____ domain (src homology)
- Grb2 has a ____ domain that binds to ____ in ____
- SOS binds to ____ and acts as a GEF (GDP → GTP)
- Ras → ____ → ____ → ____
- ultimate response: changes in protein activity or gene expression
- cytoplasmic
- growth
- dimerization
- autophosphorylation
- docking
- Grb2, SH2
- SH3, prolines, SOS
- RAS
- Raf → Mek → Erk
receptor tyrosine kinase signaling
- ligand binds and induces dimerization
- autophosphorylation occurs
- docking site
- Grb2 binds (with SH2 domain)
- SH3 domain of Grb2 binds prolines in SOS
- SOS is a GEF and adds GTP to Ras
- Raf → Mek → Erk
- ultimate response
JAK-STAT Receptors:
- ligand binds and receptors ____ , then bind ____ (Janus kinases)
- JAKs ____ each other and the receptor
- receptor binds and phosphorylates ____.
- STATs separate from receptors, ____ , and enters the ____ , binds to ____ and causes transcription
- dimerize, JAKs
- phosphorylate
- STATs
- dimerize, nucleus, DNA
serine-threonine receptor and Smad:
- ligands bind and receptors ____ and are phosphorylated
- activated receptor (by phosphorylation) binds to ____ and phosphorylates ____
- R-smad binds to ____ and moves into nucleus to impact ____
- dimerize
- R-smad, r-smad
- Co-Smad, transcription
what makes cells different
differences in proteins due to differences in gene expression
Helix-turn-helix DNA binding motif:
- ____ DNA binding motif
- ____ alpha helices connected by short chain of amino acids
- longer helix portion = ____ module-DNA
- binds to ____ groove of DNA
- binds DNA as ____
- simplest
- 2
- recognition
- major
- dimer
zinc finger motif:
- DNA binding motif includes a ____ atom
- binds to ____ groove of DNA
- includes ____ and ____ secondary structures
- zinc
- major
- alpha-helix and beta-sheet
leucine zipper motif:
- 3 domains:
- includes:
- interactions between hydrophobic amino acid side chains (leucines) at every ____ amino acids down one side of alpha helix
- grabs DNA like ____
- dimerization domain, activation domain, and DNA binding domain
- 2 alpha helices
- 7
- clothespin
helix-loop-helix motif:
- includes:
- can occur as ____ or ____
- 3 domains:
- short alpha chain connected by a loop to a second longer alpha chain
- homodimers or heterodimers
- DNA binding domain, dimerization domain, activation domain
regulation by RNA stability:
- decapping: exposed mRNA degraded from ____ end
- mRNA degraded from ____ end through polyA tail and into coding region
- 5’
- 3’
3 post translational modifications
non-covalent interactions (protein folding and cofactor binding)
covalent modification (phosphorylation, etc.)
binding to other protein subunits
proteasome:
specificity of proteasome: ____ E1 ubiquitin activating enzyme and ____ proteasome, but 30 E2 ubiquitin conjugating enzymes and hundreds of E3 accessory proteins
apparatus that deliberately destroys aberrant protein
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