Ras Map Kinase Pathway Lecture

May 31, 2024

Ras Map Kinase Pathway Lecture Notes

Introduction

  • Discussion on the Ras Map Kinase Pathway
  • Initiated at the receptor level
  • Receptor type: Receptor Tyrosine Kinase (intrinsic tyrosine kinase activity)

Ligand Binding and Receptor Activation

  • Ligands: Mitogens or Growth Factors
  • Receptor dimerizes upon ligand binding
  • Activated receptor phosphorylates tyrosine residues in the cytoplasmic domain

Docking of Adaptor Proteins

  • Specific adaptor proteins dock to phosphorylated tyrosine residues
  • Example: GRB2 (SH2 domain recognizes phosphotyrosine residues)

Interaction with SOS Protein

  • GRB2 interacts with SOS (Son of Sevenless)
  • SOS: Guanine nucleotide exchange factor
  • Facilitates GDP-GTP exchange in Ras protein

Ras Activation

  • Ras: Monomeric G protein activated through GTP binding
  • Activated Ras dissociates and interacts with Raf kinase

Raf Activation

  • Interaction between Ras and Raf
  • Activation is temporary; regulated by GAP (GTP-activator protein)
  • GAP hydrolyzes GTP, inactivating Ras

Downstream Kinase Activation

  • Active Raf phosphorylates MEK kinase
  • MEK phosphorylates ERK kinase
  • ERK translocates to the nucleus
  • ERK interacts with transcription factors and RNA polymerase

Gene Transcription

  • Genes promoting growth and division are transcribed
  • Examples: Cyclin D1, c-Myc, Bcl-2, Bcl-xL
  • Importance for tissue growth and cell division

Cyclin D and Cell Cycle Progression

  • Cyclin D partners with CDK4/6
  • Cyclin D-CDK4/6 phosphorylates pRb protein
  • Phosphorylated pRb releases E2F transcription factor
  • E2F promotes S phase gene transcription

Ras Map Kinase Pathway in Cancer

  • Mutations in Ras oncogene
  • Constitutive activation of Ras due to inability of GAP to hydrolyze GTP
  • Continuous signaling leads to uncontrolled cell proliferation
  • This can lead to cancer

Pathway Initiation by GPCR

  • Possible initiation by G Protein-Coupled Receptors (GPCR)
  • Role of Beta-Arrestin: Modulates GPCR pathway
  • Beta-Arrestin recruits Src kinase, phosphorylates ERK
  • ERK in the nucleus activates growth and proliferation genes

Crosstalk Between Signaling Pathways

  • Different pathways can interact at various levels

Conclusion

  • Importance of supporting the channel, courses available on Unacademy
  • Support options mentioned for different viewers (e.g., Patreon, GPA, UPI)

Call to Action

  • Like, share, and subscribe to the channel
  • Use provided code for accessing courses on Unacademy