More GTPases Flashcards
Ran
small GTPases which is a molecular switch involved in nuclear transport - karyopherins
Karyopherins in the cytosol
-do not bind Ran.GDP so they are free to bind cargo
Ran GTP in the nucleus
the karyopherin cargo encounters Ran GTP and is transported back to the cytosol
GAP and GEF in the nuclear exchange importance
GAP is present in the cytosol - mainly Ran.GDP here
GEF is present in the Nucleus - RanGTP mainly here
what frees the karyopherin from ran.GTP when it is returned to the cytosol
encountering GAP - changing it to Ran.GDP which the karyopherin won’t bind
what happen to RanGDP when it is freed from karyopherin
is transported back to the nucleus through its own nuclear transport receptor, and converted back to RanGTP by GEF
Nuclear transport occurs when
specific proteins interact with karyopherins in a ran.GTP dependent manor
what does SRP stand for
signal recognition peptide
GPRCs
7TM domains, change 3D structure when ligand binds, trimeric - act on GEFs to exchange GDP –>GTP
GPRCs - a and y
a and y membrane bound by lipid tails
a either bound to GTP or GDP, activation of a - dissociates from b and y and then binds independent targets
a subunit of GPRC as a GTPase
hydrolyses GTP, causes a to dissociate from target protein + recombine with BY
Gas
activates adenylate cyclase - cytomplasmin cAMP conc. is normally v low - signal turned off by phosphodiesterase
cAMP mediates effects via
PKA - phosphorylates target proteins
FAST - phosphodiesterase to ensure cAMP acts as switch
SLOW - CREB bind CRB and CRE elements on DNA upstream of target genes - target transcription
GPRCs coupled to Gaq
activate membrane bound PLC - Beta
which then acts on phosphoinositol 4,5 biphosphate - PI(4,5)P2
PI(4,5)P2
the least abundant phosphinositide in the PM (<10%)
cleaved into DAG and IP3
diacyglycerol and inositol triphosphate
DAG - diacylglycerol
stays in the membrane, immediately binds to PKC bringing it to the membrane
IP3 - inositol 3,4,5 triphosphate
interacts with the ER and relates calcium, IP3 binds gated Ca2+ ion channel in ER membrane - increases Ca2+ in cytosol - Ca2+ binds to the PKC - phosphorylates target proteins
not all PKCs require
calcium - this pathway does (Gq)
cell responses which GPCRs activate PLCb
liver - vasopressin - glycogen breakdown
smooth muscle - acetylcholine - muscle contraction
uses Ca2+
- signal during fertilisation - egg activation
- muscle cells - contraction
- heart
how is cytosolic calcium maintained at 10^-7
- Ca2+ in the ER membrane
- Ca2+ binding molecules in the cytosol
- active Ca2+ transport in the mitochondrial matrix
wat is Cam
a kinase which recognises Ca2+ spike in the heart
Ca2+/Cam kinase II initially activated by Ca2+/Cam undergoes autophosphorylation - even when Ca2+ signal lost , kinase remains - until phosphatase overwhelms
2 classes which transmit signals from RTKs
Rho and ras
RTK anchored to
the cytoplasmic face of the plasma membrane
RTK docking proteins
Grb2 and Drk bind to pTyr on receptor - brings Ras-GEF to PM - activating Ras
Ras
associates and activates a kinase - triggering MAP kinase cascade - results in phosphorylation of target proteins + cellular response
Map stands for
mitogen activated proteins
Negative feedback w. RTK - ras
activation of phosphatase and MAPK - dependent inactivation of Raf
scaffolding and docking proteins are activated by
small GTPase
what do GPRCs and RTKs lead to
gene regulation and target proteins
