Chapter Seven Flashcards
What happens once the antigen is encountered?
cellular reconfiguration: naive lymphocyte -> active cells
What happens in active cells?
- reorganize actin cytoskeleton 2. activating transcription factors 3. synthesizing a wide range of new proteins
What else is needed aside from receptor mediated signaling to activate naive T cell and naive B cells?
co-stimulatory signaling
Intracellular signaling proteins serve to
integrate incoming signals.
Signal transduction
process whereby one type of signal is converted to another
What do transmembrane receptors covert extracellular signal into?
intracellular biochemical events
Enzymes most commonly associated with receptor activation
protein kinases. How are receptors activated?
3 AAs in animals that protein kinases phosphorylate proteins on
- tyrosine 2. serine 3. threonine (we focus on tyrosine)
Intrinsic protein kinsaes
intrinsic part of the receptor
Associated protein kinases
kinase in noncovalently associated with the receptor
Receptor Tyrosine Kinases (RTK)
activate lymphocyte receptors
What is signal strength?
minimum threshold all factors must meet for signaling to occur
What do variations in signal strength determine?
magnitude of cellular responses
What does protein phosphatase do?
turns off signal via dephosphorylation (dephos does not alway turn off)
What does extent of phosphorylation of an enzyme determine?
its activity…represent a balance between activity of kinases and phosphatases
Large multiprotein signaling complexes
mediate intracellular signal propagation. made on unique enzymes + other components = signal it generates
Signaling proteins interact with each other and with lipid signaling molecules via
modular protein domains
SH2 protein domain
recognizes phosphorylated tyrosine (pY) and AA 3 positions away and binds in sequence specific fashion
Assembly of signaling complexes
mediated by scaffold and adaptor proteins (non-enzymatic). scaffolds can function to promote membrane localization of the signaling complex
Ras
small GTPase involved in many pathways leading to cell proliferation
Small G proteins
molecular switches in many different signaling pathways
Rac, Rho, Cdc42
small GTPases that control changes in actin cytoskeleton caused by signals received through the TCR or BCR
GTP binding
signals turns on: GDP out & GTP in
GTP hydrolysis
signal turns off: Phosphate pops off
Signaling by GTPA binding proteins
GTP binding turns on vs. GTP hydrolysis turns it off
Ways signaling proteins are recruited to membrane
- binding to phosphorylated site on membrane associated protein 2. recognition of activated small G proteins 3. PIP2 to PIP3 4. binding to membrane lipids
Phosphatases vs. Ubiquitination protein degradition
reversible vs. irreversible termination of signaling