BiocoreIISignaling2014preclass

Binding of hormone causes a conformaon change that

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Unformatted text preview: t property do steroids have with respect to the cell membrane? 9 nuclear receptor – cytoplasmic recep@on Type I., androgen, estrogen, progesterone, gluccoco@coid 1. Hormones very ohen are lipid soluble and cross the plasma membrane passively but not the nuclear envelope. 2. Therefore, one large class of nuclear receptors perceive the hormone signal in the cytoplasm Chaperone bound, cannot enter nucleus Ligand bound form enters nucleus 3. Binding of hormone causes a conforma@on change that allows nuclear receptor to pass nuclear membrane and act as a transcrip@on factor. Thus, a nuclear receptor has a ligand binding domain, a DNA binding domain, and an ac@va@on domain 10 TGF- β – puzzle pieces 1. TGF- β is ligand 2. Receptor is a serine threonine kinase 3. Receptors dimerize but interac@on is between two unlike Ser/Thr kinases (heterodimeriza@on) 4. Heterodimeriza@on sets up a phosphoryla@on cascade, relaying the phosphorylated state to Smad proteins “monogomous” – one set of targets - - Smads many effects but one typical effect is to control growth Can be an autocrine, paracrine or endocrine signal, e.g., BMP7 5. Phosphorylated Smads can enter the nucleus and ini@ate transcrip@on 11 Receptor Tyrosine Kinases 1.  RTKs typically func@on as dimers as well and can func@on as homo or heterodimers 2.  Different isoforms bind different ligands 3.  Important ligands in humans are Epidermal Growth Factors (EGFs) that bind Human Epidermal Growth Factor Receptors (HERs). Important Roles in Breast Cancer 12 G- Proteins 13 RAS- RAF – small G protein...
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This document was uploaded on 03/09/2014 for the course BIOLOGY biocore at NYU.

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