signalling mechanisms in growth and division Flashcards
DIAGRAM role of C-Myc
when cell is in G0, when given growth factor, c-Myc gene rises, which stimulates expression of cell cycle genes, hence cells goes into G1 phase, then into S phase
pathway upon growth factor release
growth factor released eg from hepatocytes after liver damage this stimulates receptor protein tyrosine kinase, which stimulates a G protein (RAS), which causes a kinase cascade this causes expression of early genes like C-myc, which control expression of cell cycle genes
DIAGRAM what occurs at cellular level when growth factor binds with example
forms a dimer, which phosphorylates the kinase- the phosphorylated kinase then recruit ADAPTOR proteins, which help transmit signal to start kinase cascade eg Grb2
DIAGRAM feature of adaptor proteins
have domains- Grb 2 has a domain which is proline rich, and another one which binds to phosphorylated tyrosines
G proteins
aka RAS proteins, which often become oncogenes- they are GTP binding proteins normally they bind to GDP and are off- a signal causes phosphorylation of GDP to GTP, activating it- it is then quickly inactivated by hydrolysis
how is RAS activated/inactivated
activated by exchange factors eg SOS inactivated by GAP (GTPase activating proteins)
DIAGRAM overall signal from RPTK to RAS
phosphorylated RPTK recruits grb2 adaptor protein, which recruits exchange factor Sos,which activates RAS protein, helping to transmit signal
how does Ras become an oncogene
mutations increase amount of active RAS mutations prevents GAP from binding and causing inactivation other mutations prevent GTP hydrolysis
what does active Ras do
activates protein kinase cascade, where one kinase activates another
what is ERK cascade with enzyme names
type of kinase cascade 1st kinase is Raf, 2nd is MEK, 3rd is ERK
what does these phosphorylates protein kinases do
cause change in proteins, as well as gene expression eg activate c-Myc, which along with Ras is also another oncogene
what controls cell cycle and how different parts of cell cycle stimulated
cyclin-dependent kinases (Cdks)- are activated by cyclins, which bind this is transient, so cyclins are inactivated rapidly, then other cyclins bind to trigger DIFFERENT parts o f cell cycle- thus different cycling-Cdk complexes form
DIAGRAM how Cdks are regulated+ example during interphase/mitosis
by phosphorylation- there are activating kinases (Cdk activating kinase) and inhibitory kinases Cdk1 binds to cyclin B- kinases act on it, then dephosphorylation by phosphatases activates Cdk1 at end of interphase, causing mitosis at anaphase checkpoint, cyclin B degraded, and mitosis continues
DIAGRAM other cyclins/CDKs
CDK 1 involved in mitosis, but CDK2 involved in G1/S phase- they bind to cyclin A/E
what does C myc do
causes expression of cyclin D, which binds to CDK 4/6 and causes cell to go from G0 to G1
DIAGRAM what do activated CDKs do with example
they phosphorylate certain proteins eg retinoblastoma protein in GO, active Rb protein bound to TF E2F- CDK4/6 then phosphorylates it, removing E2F, thus Rb protein inactive Rb protein thus a TUMOUR surpressor
DIAGRAM what does active E2F do
transcribes different cyclin eg cyclin E, which binds to another Cdk, activating other paprt of cell cycle- this continues
