Wnt Signaling Pathway Co-Receptors and Interaction

Cell Division and Signaling Pathways

• Cells divide to replace old or damaged cells, grow, and increase in size.
• Cell growth, differentiation, and proliferation are crucial for organism development and maintenance.

Cell Signaling

• Cell signaling is the ability of cells to receive, process, and transmit signals with their environment and themselves.
• Signals can be physical (mechanical pressure, voltage, temperature, light) or chemical (small molecules, peptides, or gas).
• Signaling molecules can be synthesized through various biosynthetic pathways and released through passive or active transport, or from cell damage.

Signaling Pathways

• 17 signaling pathways mentioned, including:
  • Akt/PKB
  • AMPK
  • cAMP-dependent
  • Wnt
  • Eph/ephrin
  • Hippo
  • Insulin signal transduction
  • JAK-STAT
  • MAPK/ERK
  • mTOR
  • Nodal
  • Notch
  • PI3K/AKT/mTOR
  • TGF beta
  • TLR
  • VEGF
  • Hedgehog

Wnt Signaling Pathway

• A group of signal transduction pathways that begin with proteins passing signals into cells through cell surface receptors.
• Wnt signaling pathways use paracrine or autocrine communication.
• Wnt signals give shape to tissues as cells proliferate.
• Misregulation of Wnt signaling can lead to tumor development via excess cell proliferation.

Wnt/β-Catenin Pathway (Canonical Pathway)

• Wnt signaling begins with Wnt protein binding to the Frizzled (Fz) family receptor.
• Co-receptors (LDL receptor-related protein 5/6) may be required alongside the Wnt protein and Fz receptor interaction.
• The signal is transmitted to Disheveled (Dsh), a protein located in the cytoplasm.
• Wnt causes the translocation of the negative Wnt regulator, Axin, and the destruction complex (APC and GSK) to the plasma membrane.
• β-Catenin accumulates and localizes to the nucleus, inducing a cellular response via regulating transcription of target genes.

JAK-STAT Signaling Pathway

• JAK-STAT signaling allows the transcription of genes involved in cell division.
• Excessive JAK-STAT signaling can lead to cancer formation.
• JAK-STAT signaling in mammary glands promotes cell division and reduces cell apoptosis, causing cancer breast.
• High STAT3 activity plays a major role in this process, allowing the transcription of genes involved in cell division.
• Mutations in JAK2 cause leukemia and lymphoma.

JAK-STAT Mechanism

• The binding of cytokines (interleukin and interferons) to cell surface receptors causes the receptors to dimerize, bringing the receptor-associated JAKs into close proximity.
• JAKs phosphorylate each other through transphosphorylation, increasing their kinase domain activity.
• Activated JAKs then phosphorylate tyrosine residues on the receptor.
• STATs bind to the phosphorylated tyrosine on the receptor and are tyrosine-phosphorylated by JAKs, causing the STATs to dissociate from the receptor.
• Activated STATs form hetero or homodimers, translocating to the nucleus to induce transcription of target genes.