Most cell signaling pathways eventually regulate gene expression by regulating t

Question

Most cell signaling pathways eventually regulate gene expression by regulating transcription factors in the nucleus. In class, we have discussed several pathways (e.g. Wnt, SMAD, NFkB, cAMP-dependent signaling, MAPK pathway, and Notch signaling) that result in transcriptional regulation by sending a protein into the nucleus. Choose 3 of these pathways and discuss: what the protein is that enters the nucleus, how it is activated by its signaling pathway, and whether the activated protein that enters the nucleus is directly responsible for binding to DNA or whether it exerts its effects by regulating transcription factors. Be specific and explain your answer.

Explanation / Answer

1: MAPK pathway: The dimeric form of the active MAP kinase enter the nucleus and activated many transcription factors. MAP kinase is activated by Ras protein. The inactivated Ras protein is found bound to GDP. Binding of its ligand to the cytokine receptor of Ras protein forms activated Ras-GTP complex which in turn serve to activate the MAP kinase through activation of Raf (Rapidly Accelerated Fibrosarcoma) and MEK (Mitogen-activated protein kinase).

2: Notch pathway: Notch proteins are the ion channels which are activated upon binding of delta or serrate proteins that serve as ligands. Upon binding of ligand, the cytosolic segment of the protein is released from the receptor transmembrane domain. The released cytosolic segment enter the nucleus and serve as co activator of transcription factors.

3: Wnt pathway: These are the ion channels for which secreted Wnt (in mammala) or Wg (Drosophila) serve as ligand. A Frizzled protein which have seven transmembrane alpha helices serve as receptor for the ligands. Binding of Wnt ligand to receptor activated the Frizzled which in turn serve to activate the cytosolic protein Dishevelled. The activated protein serves to allow the beta catenin to escape from beta catenin degradation complex. Beta catenin enters nucleus and regulate the gene expression by directly binding to the promoters or enhancers of gene.

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