8 - Growth Factors and Signal Transduction Flashcards
How do growth factors affect cell division?
(proliferation) accelerates it = cell grows more aggressively
What are the 4 cell responses to signals? Which cells will respond to certain signals?
(SDDD) survive | differentiate | divide | die | only cells with the receptor of that signal
What is hypertrophy?
cells growing in size
What is the difference between cell growth and cell proliferation?
growth = increase size | proliferation = increase numbers/copies (multiply)
How can a cell grow independently?
allows access to a growth hormone that will activate division machinery
What is prolong ligand-induced signaling?
decrease degradation of pathway proteins, turn off negative regulators
What are the 5 ways a cell can achieve extrinsic factor (outside cell signaling) independence?
prolong ligand-induced signaling | increase sensitivity (respond to lower ligand levels) | express new receptors | signal in absence of ligand (induce mutations) | make own growth factors
Why would a tumor cell want to be independent of extrinsic factors?
the signal stimulation is not permanent = need more of it | signals are not always present = need to wait for it to come
What are autocrine loops and paracrine loops? Which ones do tumor cells most use?
autocrine (most used by tumors) = secrete own growth factors and stimulate self | paracrine = stimulate other cells, help others grow
What are cytokines?
proteins and peptides used as signaling compounds
What type of signal are tumor growth factors?
cytokines
What cellular responses do cytokines induce?
protein modification and gene activation
What is HER-ceptin?
targets breast cancer cells that express HER proteins via a signaling network
What enables a ligand-receptor interaction to give rise to multiple cellular responses/effects?
amplification in signaling pathway | a signal in the pathway will hit different types of proteins»_space;> different cellular effects/responses
What is phosphorylation of a protein?
adding a phosphate onto a protein = protein undergoes conformational change = either turns it on or off
On which 3 amino acids will a protein be phosphorylated?
tyrosine, serine, threonine
What enzyme adds a phosphate from ATP onto protein?
kinase
What enzyme takes a phosphate from a phosphorylated protein?
phosphatase = dephosphorylate
How does phosphorylation of a protein change the interaction within the amino acids of a protein?
phosphate = highly negative = can cause major repulsion = can open up active sites
What effect does the signaling pathway have on tumor suppressors or proto-oncogenes?
can activate or deactivate them
What is the effect of a mutation in the p53 gene?
it is unable to activate genes that encode for the protein needed to stall cell division = this protein is not made = cell division not stalled
What type of gene (tumor suppressor or proto-oncogene) is the Ras gene?
proto-oncogene
What is the effect of a mutation in the Ras gene?
it will send out growth signals in the cell on its own without a signal stimulating receptor = cell replicates excessively
What are the 6 types of proteins encoded by proto-oncogenes?
growth factors and its receptors | protein kinases and those that activate it | cell cycle proteins | apoptotic proteins | transcription factors
What are the 2 major classes of tumor utilized surface receptors?
enzyme linked | G-protein linked
What are the 3 cellular effects if JAK/STATs pathways?
cell growth | immune response | differenitation
What are the 3 levels of the MAP kinase cascade? (order them from first to last)
MAP-KKK | MAP-KK | MAP-K | activates other proteins or causes gene expression
What are the 7 cellular effects of MAP kinase cascades?
cell growth | apoptosis | angiogenesis | energy deregulation | development | differentiation
What is cross-phosphorylation?
dimers will cross phosphorylate each other = conformational change = adapter domains available for other proteins to latch on
What is an example of an adapter domain?
SH2 domain
How can 1 receptor have 5 outcomes?
domino effect »_space;> can split and activate multiple pathways
What is the mechanism of redundancy in receptor subunits?
different cytokine receptors share a common subunit = allows for different combinations of receptors = doesn’t need to make new receptors all the time
What type of protein is STAT?
transcription factor puts RNA pol on DNA and helps turn genes on
What type of protein is JAK?
receptor kinase
What is EGF and what does it do?
epidermal growth factor | binds to JAKs and causes it to dimerize
For a gene to be expressed, what needs to be there other than RNA polymerase?
transcription factors = recruits RNA pol onto DNA
What is delayed gene expression?
transcription factors MUST be expressed first (immediate gene expression) before expressing desired genes (delayed gene expression)
What are 2 ways that tumors deregulate receptor signaling?
via autocrine loop signaling | mutate receptors to initiate signaling cascade in absence of growth factor
