Perrino GPCRs second half Flashcards
Signaling proteins with (blank) domains bind to P04-Y docking sites on an activated (blank) receptor
SH2
PDGF
A PDGF receptor has a split tyrosine kinase domain that can be phosphorylated via what three things?
PI3 kinase, GAP, PLCgamma
Phosphorylated Tyr serve as docking sites for protein with (blank) domains
SH2
The monomeric G protein(blank) provides a crucial link between receptor Tyr kinases and the downstream signaling cascades
Ras
When ras is bound to (blank) it is active.
gtp
The active Ras protin activates what pathway?
the map kinase pathway
Describe the MAP kinase pathway:
Active Ras bound to GTP activates MAP kinasekinase kinase (RAF) which phosphorylates MAP kinase kinase (Mek) which phosphorylates a Map kinase (Erk) which phosphorylates proteins and gene regulatory proteins to either change gene expression or protein activity
How does Ras get activated to gain a GTP?
Via Ras GEF
What does GAP do to Ras?
dephosphorylates it making it bind to GDP instead of GTP
Why is there generation of PIP2 and PIP3 by PI3 kinase?
to generate docking sites for signaling
proteins that have PH domains
Describe the PI3 signaling pathways:
activated B cell receptor->activated PI-3 kinase->activated PIP2-> PIP3->phosphorylates PH domains ( activates PLC-gamma, and BTK)-> activates PIP2-> IP3_> activation of PKC and release of Ca2+ from ER.
What makes this happen:
activation of down steam pathways, clonal expansion, activation of immunoglobin promotors, translation of antigen specific immunoglobins, regulated exocytosis of immunoglobulins into circulation.
Relase of Ca2+ from the ER via the PI3 kinase signaling pathway
(blank) is an inherited disorder characterized by very low levels of protective immunoglobulins.
affected individuals develop repeated infections.
such as Hemophilus influenzae, pneumococcus (Streptococcus pneumoniae), and staphylococci as well as repeated viral infections. The upper respiratory tract, lungs, and skin are common sites of infection.
X-linked agammaglobulinemia
What disease has frequent infections, conjuctivitis pneumonia brochitis skin inections, diarrea and can be detected via serum immunoglobulins. People with this disease are treated with influsions of blood plasma and serum immun globulin.
X-linked agammaglobulinemia
What is the apoptosis pathway with PI3 kinase and Akt?
activated TyrK receptor->activates PIP2-> PIP3-> phosphorylates Akt and PDK1-> Akt is activated by PDK1 and mTOR-> Akt dissociates -> may or may not phosphorylate Bad-> apoptosis or if phosphorylated inhibitory protein prevents apoptosis.
What is the purpose of the Jack-STAT pathway?
rapid delivery of cytokine signaling to nucleus
Describe the Jack-STAT pathway
cytokin receptors bind cytokine-> dimerization->JACKs cross phosphorylate-> JACKs phosphorylated receptor-> Stats dock on receptor-> JACKs phosphorylate STATS-> Stats dissociate from receptor and dimerize via SH2 domains-> STATS go to nucleus and activate gene transcription.
What is the TGF-beta and SMAD pathways good for?
during development:
- pattern formation
- specification
- ECM production
during adulthood:
- tissue repair
- immune regulation
Described the TGF-beta and the SMAD pathway
type II and type I tgf receptors dimerize, the serine/threonine kinase domain on type II phosphorylatse type I receptor-> type 1 receptor phosphorylatse SMAD2 or SMAD3-> SMADs dissociate and oligomerizes with SMAD4 and moves to nucleus-> activates gene transcription and makes smad 6 and
What are the major proteolysis-dependent signaling pathways?
Notch mediated, Wnt mediated, hedgehog, NF-kB
Rheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production of inflammatory mediators in the synovium mediated, in part, by the transcription factor (blank).
NF-kappaB.
Describe the NF-kB pathway?
TNF alpha Trimer binds to TNF alpha receptor, which activates IKK complex which phosphorylates IkB, IkB then gets degraded and IkB is liberated and translocation into nucleus to activated transciption NFkB target genes.
What is Chronn’s disease iniated by?
What is it driven by?
inappropriate innate and acquired immune responses to normal enteric flora.
driven by pro-inflammatory TNF macrophage-dependent chronic activation
(blank) blocks the actions of TNF-a by binding to it and preventing it from signaling to its receptors on the surface of cells.
Infliximab (remicade)
What kind of receptors are these?
PI3 kinase, PLC-g, IP3, Ca2+
Src
Jak-STATs
NF-kB
enzyme linked
What kind of receptors are these?
Smads
rSer/Thre kinases
What kind of receptors are these:
Ras, MAP kinase
rPTKs
What kind of receptors are these: Ga cAMP adenylyl cyclase PKA Gi inhibition of adenylyl cyclase Golf cAMP Na channel Gq PLCb DAG IP3 Ca2+ Gt inhibit PDE increase cGMP
GPCRs
