15998718
Signal Transduction Lecture 1
- Principle: signal --> Receptor --> Signal transduction --> Effector Protein --> mod cell function/gene
expression
- Ligand --> receptor --> conformational
change
- Intracell Receptors
- Ligand --> receptor --> conformational
change
- 3 Paths
- Endocrine
- Autocrine
- ACh
- DA
- 5-HTS
- NE
- Endorphins
- ACh
- Paracrine
- Endocrine
- E.g.:, RECEPTOR TYROSINE KINASE (TK)
- Encoded by multigene family
- 20 human RTK
families
- 20 human RTK
families
- Pathways
- Insulin
- CONSERVED: insulin/insulin-like signaling growth factor signaling (IIS)
- Growth + dev't
- Metabolism
- Stress
Response
- Longevity
- uptake ions
- Carb, lipid, protein
metabolism
- Glu uptake +
gluconeogenesis
- Lipogenesis, protein syn, glycogen
syn
- Glycolysis
- Glu uptake +
gluconeogenesis
- Growth + dev't
- Fun Facts
- First hormone
isolated/ID'd
- Mech not completely
known
- Getting Insulin
- First hormone
isolated/ID'd
- Org Paths
- Drosophila
- DILP (drosophila insulin-like
peptide)
- 8 DILPs + 1 insulin receptor
(DInR)
- B-C-A structure
conserved
- Homologous to mammalian
insulin
- Homologous to mammalian
insulin
- DILP 7: structurally similar to
preproinsulin
- DILP 7: structurally similar to
preproinsulin
- Animal dev't + energy
homeostasis
- 8 DILPs + 1 insulin receptor
(DInR)
- DILP (drosophila insulin-like
peptide)
- C. elegans
- IIS responds to environ. signals
- IIS responds to environ. signals
- Mammals
- Drosophila
- CONSERVED: insulin/insulin-like signaling growth factor signaling (IIS)
- Insulin
- Family
- IR
- Mutations
- IR
resistance; heterozygous = less severe
- normal intrauterine growth; die acidosis at 3-7
days (SO, need IR post-natally only)
- normal intrauterine growth; die acidosis at 3-7
days (SO, need IR post-natally only)
- 1. Less syn
- 2. Inhibit intracell transport
- 3. Less affinity to
insulin
- 4. Inhibit TK
- 5. Degrade faster
- Donohue Syndrome: IR mutation --> low growth, hypoglycemic, death at 1-2 yrs old, no treatment; chromosome 19
- IR
resistance; heterozygous = less severe
- Mutations
- IGF-1R
- dysfunction: low intra-uterine + postnatal growth; normal glu
- dysfunction: low intra-uterine + postnatal growth; normal glu
- IRR (insulin receptor related receptor): Orphan
receptor
- IR
- Domains
- Extracell
- alpha + 1/3 beta
- Ligand binding domain (alpha)
- alpha + 1/3 beta
- Transmembrane
- Intracell
- Juxtamembrane
- TK domain
- Activated by IR conformation change
- Transautophosphorylation
- Activated by IR conformation change
- C-terminus domain
- Juxtamembrane
- Extracell
- Encoded by multigene family
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