Cell Signaling Part 3 2024

Chapter 16: Cell Signaling

General Principles of Cell Signaling

  • Cell signaling is crucial for coordinating cellular functions and responses to environmental stimuli.

  • Two main types of receptors involved: G-Protein Coupled Receptors (GPCRs) and Enzyme-Coupled Receptors.

Enzyme-Coupled Receptors

Overview

  • Enzyme-coupled receptors receive signals from molecules, typically in dimeric form.

  • Inactive receptor → Active receptor after binding.

  • Often have associated enzymatic domains which become activated upon receptor activation.

Receptor Tyrosine Kinases (RTKs)

  • Largest class of enzyme-coupled receptors.

  • Activation leads to assembly of intracellular signaling complexes.

Activation of RTKs

  • Activation Process:

    • Signal molecule in the form of a dimer binds to the receptor.

    • Causes phosphorylation of tyrosine residues in the intracellular domain.

  • Effects:

    • Stimulates downstream intracellular signaling pathways through activated RTKs.

RTK Signaling Pathways

Ras Activation

  • RTK activates the monomeric GTPase Ras.

  • Process:

    • Inactive Ras binds to activated RTK and exchanges GDP for GTP.

    • This promotes signal transmission.

MAP Kinase Signaling Module

  • Activation Flow: Ras → MAP kinase kinase kinase → MAP kinase.

  • Changes in protein activity and gene expression occur as a result of this signaling cascade.

PI-3-Kinase-Akt Pathway

Inhibition of Apoptosis

  • RTKs can activate the PI-3-kinase-Akt signaling pathway, promoting cell survival.

  • Mechanism:

    • Activation of Akt → phosphorylation of Bad → inhibition of apoptosis by promoting release of active Bcl2.

Cell Growth Stimulation

  • Akt also stimulates cell growth by activating the TOR kinase.

  • Promotes protein synthesis and inhibits degradation, thus promoting overall cell size increase.

Integrated Signaling from GPCRs and RTKs

  • Both GPCRs and RTKs can activate multiple intracellular signaling pathways.

  • Diverse targets including phospholipase C, PI-3-kinase, and MAP kinases.

Use of Mutant Proteins

  • Studying mutant proteins can elucidate binding sites and pathways of intracellular signaling molecules.

  • Helps in understanding how specific mutations affect signal transduction.

Notch Signaling Pathway

Overview

  • Notch signaling plays a crucial role in nerve cell development in Drosophila.

  • Involves interaction with Delta signal protein leading to cell specialization and lateral inhibition.

Mechanism

  • Notch receptor acts as a transcription regulator, activating responsive genes upon binding with Delta.

Intracellular Receptors for Small Hormones

Hormones and Receptors

  • Small, hydrophobic hormones (like cortisol) bind to intracellular receptors that act as transcription regulators.

  • Hormonal signaling pathway includes moving into the nucleus and activating transcription of target genes.

Plant Signaling Strategies

Differences from Animal Systems

  • Plants utilize distinct signaling strategies, including enzyme-coupled receptors and serine/threonine kinases.

  • The ethylene signaling pathway: turns on genes by relieving inhibition when ethylene is present.

Integrating Signals

  • Intracellular signaling proteins serve to integrate multiple incoming signals to produce an appropriate cellular response.