Lecture 25 - Cancer Flashcards
name 4 mechanisms by which tumour cells contribute e-cadherin loss
- degredation by mmp3 protease
- suppression of e cadherin synthesis
- enchanced e-cadherin ubiquitination by tyrosine
- phosphorylation via c-src kinase action
to what motif to integrin receptors bind to?
RGD motifs, arg, gly, asp
what kind of dimer is integrin and what is their affinity for one another?
it is a heterodimer of alpha and beta chains, their affinities are low, allowing for a dynamic interaction
true or false
erbB2 receptor has no ligand, yet somehow continues to signal?
true
which receptor does herceptin target?
erbB2
what kind of dimer(s) can the erbB receptors form, and what occurs as a result?
they can form both homo and heterodimersthis activates their cytosolic domain, which has a tyrosine kinase. this results in reciprocal phosphorylation of their cytoplasmic tails (transphosphorylation)
what is the benefit of erbB receptors being able to form dimers and why is its overexpression beneficial to tumour cells?
it allows a limited number of ligands to activate many receptors
describe how a tumour cell can utilise an autocrine pathway to benefit further from overexpressed erbB receptors
by producing even more ligands that can already act on many receptors, the cell growth signal is amplified greatly
how can erbB receptors be turned off?
dephosphorylating their cytoplasmic tails
what happens when an extracellular domain is missing in erbB receptors, and does this mutation occur in humans?
the receptor is constitutively active. fortunately, this doesnt occur in humans
where at the cytoplasmic tails does tyrosine kinase phosphorylate?
it phosphorylates the many tyrosine residues found along the cytoplasmic tail
describe how PIs can act as second messengers, and describe what feature allows many diverse roles
the inositol unit of the PI can be phosphorylated at different carbons. This is highly specific and typically requires its own enzyme to do so. This allows it to act as a second messenger with high capability for diverse roles
to what domain of EGFR does phospholipase gamma bind to, and what occurs when it does?
SH2 domain. upon binding, PLC gamma is phosphorylated by EGF receptor kinase.
what is the function of an active PLC gamma?
it cleaves off the inositol unit to result in a diacyl chain and free inositol
what is the function of a diacyl chain following cleavage of its inositol unit?
typically activates protein kinase C which promotes cell growth
