17.4 Receptors Coupled to Transcription Factors Flashcards
prototype of a polypeptide growth factor family that controls proliferation and differentiation of a variety of cell types
TGF-beta (transforming growth factor)
TGF-beta receptors are composed of 2 distinct polypeptides () that become associated following ligand binding
type I and type II
overview of TGF-beta/Smad pathway
- TGF-beta binding leads to association of type I and II polypeptides of TGF-beta receptor
- type II receptor phosphorylates type I receptor
- type I receptor phosphorylates transctiption factors of the Smad family
- phosphorylated Smads form complexes that translocate to the nucleus and
similarities of TGF-beta/Smad and JAK/STAT pathways
- both involve a protein kinase associated with a receptor that directly phosphorylates and activates a transcription factor
- both involve dimerized components
- both result in expression of target genes in the nucleus
differences of TGF-beta/Smad and JAK/STAT pathways
- receptors of transforming growth factor beta (TGF-beta) and related polypeptides are protein kinases that phosphorylate serine or threonine residues
- receptors in JAK/STAT pathways phosphorylate tyrosine residues
family of transcription factors that stimulates ubiquitylation and degradation of an inhibitory subunit
NF-kappaB family
NF-kappaB family consists of 5 transcription factors that play key roles in the (1), as well as in (2)
- immune system and in inflammation
- regulation of proliferation and survival of many animal cell types
NF-kappaB family members can be activated by:
- cytokines
- growth factors
- bacterial/viral infections
- DNA damage
signaling pathways that lead to NF-kappaB activation were found downstream of:
- tumor necrosis factor (TNF)
- Toll-like receptors - recognize a variety of molecules associated with pathogenic bacteria and viruses
cytokine that induces inflammation and cell death
tumor necrosis factor (TNF)
receptors that recognize a variety of molecules associated with pathogenic bacteria and viruses
Toll-like receptors
overview of NF-kappaB pathway
- bound inhibitory I(kappa)B proteins maintain NF-kappaB proteins in an inactive state in the cytosol of unstimulated cells
- activation of TNF and Toll-like receptors results in recruitment of adaptor proteins that activate I(kappa)B kinase
- I(kappa)B is phosphorylated, and is thus targeted for ubiquitylation and degredation by the proteosome
- NF-kappaB is now free to translocate to the nucleus and induce target gene expression
signaling system that activates transcription factors by inhibiting their ubiquitylation and degradation (done through proteoysis)
Wnt pathway
secreted factors that control events in the development of vertebrate and invertebrate embryos, as well as in regulating the proliferation of stem cells in adult tissues
Wnt family
members of the Wnt family are secreted growth factors that bind to a complex of receptors of the (1) and (2) families
- Frizzled
- LRP