Exam 2 pt3 Flashcards
Grb2 binds the RTK on it’s _ domain
SH2
Ras GEF binds to _ at the _ domain
Grb2 at the SH3 domain
RTK →
Grb2 → Ras GEF → Ras P → MAPK
PI3 K → PI3P3 → PDK → Akt K
TGF beta binds →
SARA anchors Smad → R Smad phosphorylayion → regulate transcription
The _ domains of transmembrane enzyme-coupled receptors bind _
- extracellular: signal molecules
- intracellular have enzyme activity or directly associate with enzyme
receptor protein kinases…
phosphorylate specific tyrosine residues on both themselves and on specific intracellular signaling proteins
Initial activation of RTKs occurs when
ligand binding brings two receptors into close proximity to form dimers
RTK activation leads to dimer formation which leads to
whole process
- active receptors cross phosphorylating each other’s tyr
- forms docking sites
- intracellular signaling proteins bind to docking site
- creates signaling complezes
Intracellular signaling
proteins containing _ bind to the
docking sites and create signaling complexes
phosphotyrosine-binding domains (SH2 or PTB domains)
Docked intracellular signaling molecules are activated by
phosphorylation, conformation changes induced by binding to
the receptor, or by coming into close proximity with the next molecule in the signaling pathway
Ras proteins are linked
to the cytoplasmic surface of the plasma membrane via one or more covalently attached lipid groups
Ras inactivation a result of
- tyr specific protein phosphatases turn off RTK receptors
- Ras GAPs increase GTP hydrolysis
Ras signaling is often required for
the stimulation of cell proliferation or differentiation
Cancer cells have Ras molecules
that are constantly active because they are locked in GTP bound state so they keep proliferating
MAP is composed of
3 protein kinases
* Raf, Mek, Erk
* MAPKKK, MAPKK, MAPK
MAPK phosphorylates
many proteins
signal pathways are kept seperate by _ because
scaffold proteins because MAP modules use same enzymes for different responses in the cell so cant have cross talk
The PI-3-kinase-Akt signaling pathway plays a key role
in promoting the survival and growth of
many cell types
PI 3 Kinase pathway
while thing
- Activated RTKs recruit and activate PI 3-kinase.
- Activated PI 3-kinase phosphorylates the phosphoinositide PIP2 to produce PIP3.
- Two serine/threonine kinases, Akt and PDK1 are brought into close proximity by binding to PIP3 via PH domains.
- Akt is phosphorylated on a serine by a third kinase, mTOR, resulting in a conformational change which now allows Akt to be phosphorylated on a threonine by PDK1.
- Activated Akt dissociates from the plasma membrane and phosphorylates various target proteins.
one target of Akt is _ which _ when not phosphorylated. Akt phosphor by _
One target of Akt is the
cytosolic protein Bad which, in its non-phosphorylated state,** promotes cell death via
apoptosis**. Phosphorylation of Bad by Akt creates phospho-serine-binding sites for a
scaffold protein called 14-3-3. Binding to 14-3-3 sequesters Bad, keeping it from acting and
thereby promoting cell survival.
JAK pathway
- two JAK brought lose together
- transphosphorylation increases activity levels
- phosphorylation from active JAKs to make docking sites
- STATs bind to these sites
- phosphorylated STATs disassociate
- STAT form dimer and go to nucleus
JAK and STATs are inactivated when
tyrosine phosphatases dephosphorylate their phosphotyrosines
The JAK-STAT pathway provides one of the
most direct routes from cellsurface receptors to the nucleus and altered gene transcription.
TGF beta binding pathway
- TGF beta protein binds to receptor 1 and 2
- this brings receptors together
- Type 2 receptors phosphorylate type 1
- activated type 1 directly bind and activate Smad family protein
- receptor and Smad complex endocytosed
