Chapter 15 - Cell Communication Part 2: RTKs Flashcards
What are the main types of enzyme-coupled receptors?
Receptor Tyrosine Kinases (RTKs), Tyrosine-Kinase-associated receptors, Receptor Serine/Threonine Kinases.
Describe the key structural feature of RTKs.
Single transmembrane domain with intrinsic tyrosine kinase activity in the cytosolic domain.
How are receptor tyrosine kinases (RTKs) activated?
By ligand binding, dimerization, and trans-autophosphorylation.
What is the role of SH2 domains in RTK signaling?
They bind phosphorylated tyrosine residues, recruiting signaling proteins.
What types of domains bind to phosphorylated tyrosines on RTKs?
SH2 and PTB domains.
Explain the MAPK pathway steps after Ras activation.
Ras activates Raf, which phosphorylates MEK, leading to ERK activation and gene expression.
How does PI3K/Akt signaling contribute to cell survival?
By phosphorylating and activating Akt, which promotes survival and growth.
What is the function of PTEN in the PI3K pathway?
PTEN dephosphorylates PIP3, inhibiting the PI3K/Akt signaling pathway.
Describe the structure of G-protein coupled receptors (GPCRs).
Seven transmembrane domains that activate G proteins upon ligand binding.
How do GPCRs amplify signals?
By activating G proteins that generate second messengers like cAMP, IP₃, and DAG.
Name two common second messengers in GPCR signaling.
cAMP and IP₃.
What enzyme produces cAMP in response to GPCR activation?
Adenylyl cyclase.
Explain the role of IP₃ in GPCR signaling.
IP₃ binds to receptors on the ER, releasing Ca²⁺ into the cytosol.
How does DAG function in signal transduction?
It activates protein kinase C (PKC) to modulate cellular responses.
What is the JAK-STAT pathway primarily activated by?
Cytokine receptors associated with JAK kinases.
What happens when JAKs are activated?
They phosphorylate STAT proteins, which dimerize and translocate to the nucleus to initiate transcription.
How do receptor Serine/Threonine kinases signal?
By phosphorylating Smad proteins in response to TGF-β signaling.
What is the role of scaffold proteins in MAPK signaling?
They organize kinase complexes to prevent pathway cross-talk.
How does Ras function as a molecular switch?
It is active when bound to GTP and inactivated when hydrolyzing GTP to GDP.
What is the role of GEFs in Ras activation?
GEFs exchange GDP for GTP on Ras, activating it.
Why are Ras mutations common in cancers?
Mutations lock Ras in an active state, promoting uncontrolled cell growth.
How does the PI3K/Akt pathway contribute to cancer?
Overactive PI3K or loss of PTEN leads to prolonged cell survival and growth.
Describe EGFR’s role in oncogenesis.
EGFR mutations or overexpression lead to constant RTK signaling, promoting cancer.
What is regulated proteolysis in signaling?
A mechanism where proteolysis releases and activates key transcription factors.
Which pathways depend on regulated proteolysis?
Wnt/β-Catenin, TNF/NF-κB, and Hedgehog pathways.
How is β-Catenin regulated in the Wnt pathway?
Wnt binding prevents β-Catenin degradation, allowing it to activate target genes.
Describe the NF-κB pathway activation.
TNF binding leads to IκB degradation, releasing NF-κB to enter the nucleus.
What role does Hedgehog signaling play in development?
It regulates gene expression crucial for tissue patterning.
How does cyclopamine affect the Hedgehog pathway?
It inhibits the pathway, causing developmental defects.
How are tyrosine phosphatases involved in feedback regulation?
They remove phosphates from tyrosines to turn off RTK signaling.
Explain the role of ubiquitination in receptor downregulation.
It tags receptors for internalization and degradation in lysosomes.
How does mTOR contribute to cell growth?
It promotes protein synthesis and cell growth in response to Akt signaling.
Describe the structure of the insulin receptor.
It consists of two α and two β chains linked by disulfide bonds.
How does the insulin receptor activate glucose uptake?
By activating the PI3K/Akt pathway, leading to GLUT4 translocation to the membrane.
What is the function of Src kinases?
Non-receptor tyrosine kinases that mediate immune cell signaling.
How are Src family kinases regulated?
By SH2 and SH3 domain interactions that control kinase activity.
What impact does a PTEN mutation have on cellular signaling?
Loss of PTEN prolongs PI3K signaling, leading to excessive cell survival and growth.
How do GPCRs affect cardiac function?
By regulating ion channels to control heart rate and contraction strength.
What is cross-talk in cell signaling?
Interaction between different signaling pathways that can lead to interference.
What is the role of Gq protein in GPCR signaling?
It activates phospholipase C, producing IP₃ and DAG.
How does PI3K activation affect the plasma membrane?
It phosphorylates PIP2 to PIP3, creating docking sites for signaling proteins.
Why are tyrosine phosphorylations rare but significant?
They are mitogenic and essential for cell proliferation control.
What initiates the transcriptional response in the JAK-STAT pathway?
Phosphorylated STAT dimers translocate to the nucleus.
How does EGFR overexpression contribute to cancer?
It leads to excessive cell proliferation due to constant signaling.
Name a common signaling pathway activated by growth factors.
The PI3K/Akt pathway for survival and growth.
How does mTORC1 influence cell metabolism?
It increases protein synthesis and inhibits degradation.
What are Smad proteins?
Transcription factors activated by receptor Serine/Threonine kinases in TGF-β signaling.
How does ubiquitin tagging affect RTKs?
It marks them for degradation, controlling signal intensity.
Describe a common pathway disrupted in cancer cells.
The PI3K/Akt pathway, often due to PTEN mutations.
What is the function of phosphatases like PTPs?
They deactivate signaling pathways by removing phosphate groups.
