Ch 5: Growth Factors, Receptors, and Cancer

What is crucial for the existence of multicellular organisms in terms of cell function?

Individual cells must work in a coordinated fashion.

What is central to the formation of cancer according to the lecture?

Deregulation of cell signaling.

What enzyme does Src operate as?

Src operates as a protein kinase.

What is the main function of a protein kinase?

Transfers phosphates from ATP to other proteins in the cell.

What type of residues do most protein kinases phosphorylate?

Threonine or serine residues.

How does Src function differently compared to most protein kinases?

Src functions as a tyrosine kinase, attaching phosphates to tyrosine residues.

What triggers dimerization of receptor tyrosine kinases (RTKs)?

Binding of a growth factor ligand to the N-terminal ectodomain of a cognate receptor.

What is the result of receptor dimerization in RTKs?

Activation of each monomer's kinase and phosphorylation of the partner's tyrosines.

Why is the dimerization model important in cancer formation?

Over-expression of growth factor receptors leads to frequent dimerization and mitogenic signal emission.

What effect do mutations in the RTK domains have?

They may create ligand-independent firing, leading to unregulated signaling.

What does a truncated ectodomain of EGF-R cause?

It cannot recognize its ligand but still emits growth-stimulatory signals constitutively.

What is an autocrine signaling loop as exemplified by the Sis oncoprotein?

A cell manufactures a mitogen to which it can also respond.

Which receptors lack tyrosine kinase domains and rely on JAK tyrosine kinases?

Cytokine receptors.

What residues do TGF-B receptors phosphorylate?

Serine and threonine residues.

How does the Notch receptor activate its signaling?

It relies on proteases to liberate a cytoplasmic domain fragment that migrates to the nucleus.

What does the Patched-Smoothened system do?

It relies on one transmembrane protein controlling another to regulate transcription.

What do binding of canonical Wnt factors trigger?

It prevents a cytoplasmic kinase from destroying B-catenin.

What do G-protein-coupled receptors (GPCRs) induce?

They induce heterotrimeric G-proteins to flip from inactive GDP state to signaling GTP state.

What role do integrins play in cells?

They link cytoplasmic domains to the actin cytoskeleton and pass information in and out of the cell.

What happens upon ligand binding to integrins?

Integrins form focal adhesions.

How were Ras proteins connected to RTK signaling pathways?

The biochemical mechanisms connecting them were obscure and unclear.

What is an example of a growth factor receptor mentioned in the lecture?

Epidermal growth factor receptor (EGF-R).

What type of signaling do RTKs activate?

Mitogenic signaling.

What is the consequence of tyrosine phosphorylation in signaling?

It allows for the activation of downstream target proteins.

What is the function of the cytoplasmic domain in RTKs?

To be phosphorylated by activated kinases, emitting growth signals.

In cancer, how does receptor over-expression contribute to cell signaling?

It increases the frequency of receptor dimerization and signaling.

What type of protein does the Sis oncoprotein resemble?

A PDGF-like protein.

How can gene fusion events affect EGF-R?

They may create receptors that signal continuously.

What are the characteristics of integrins?

They are heterodimeric transmembrane receptors that interact with extracellular matrix components.

How does the binding of growth factors influence receptor activation?

It induces receptor dimerization leading to activation of kinase activity.

What is the role of JAK kinases in cytokine receptor signaling?

They provide the signaling function for cytokine receptors.

What is one possible mutation effect in the transmembrane domain of receptors?

It can lead to constant activation and growth signaling.

In cancer biology, what is the significance of the term 'pleiotropically'?

Refers to multiple biological changes occurring due to a single factor.

Which signaling pathway is favored by tyrosine phosphorylation?

Mitogenic signaling pathways.

What mechanism does the Notch receptor use to activate gene expression?

It releases a fragment that migrates to the nucleus.

What do we call the signaling loop when a cell releases a mitogen and responds to it?

Autocrine signaling loop.

What is the major finding regarding Ras proteins in this context?

Their connection to RTK signaling was not clearly understood.

What type of state do G-proteins switch to upon activation by GPCRs?

From an inactive GDP bound state to a GTP-bound signaling state.

Why is the study of RTKs important in cancer research?

They play a critical role in cell growth and signaling, impacting cancer development.

What resolves how receptors communicate signals from outside to inside the cell?

The mechanism of receptor dimerization and subsequent phosphorylation.

How do mutations in the RTK ectodomain affect receptor function?

They can lead to ligand-independent signaling.

How do high levels of RTK affect plasma membrane interactions?

They increase chances of receptor dimerization through collisions.

Why are integrins crucial for cellular communication?

They facilitate connections between the cytoskeleton and extracellular signals.

What is the overall role of cellular signaling in multicellular organisms?

To ensure coordinated functions of cells for survival and health.