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MAPK: swiss army knife of receptors

step 1: dimerization when ligand binds

unable to auto-phosphorylation

phosphorylates via Ykinase

step 2: intracellular signaling proteins bind

scaffold proteins bind SH3 domain

requires POSH

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Ligand - tyrosine kinase response - dimerization - cross phosphorylation - recruitment of scaffold proteins

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Traditional activation

Ligand - receptor dimerization - cross phosphorylation - recruitment of GRB2 SOS - activated RAS (GTP) - protein kinase

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Dimerize TKR, Phosphorylate, Then GRB2, SOS, then Ras GDP are recurited. Ras --> Raf --> MEK --> ERK. Then BOOOM CELL GROWTH

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Ligand binding, Dimerization, Cross phosphorylation, SOS, Ras, RAF, MEK, MAP, cell growth

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Can you briefly summarize the 3 steps of MAPK?

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Ligand binds, dimerization of tyrosine kinase receptor, cross phosphorylation, GRB2 and SOS, ras! Cell proliferation! 

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Ligand binds, dimerization of tyrosine kinase receptor, cross phosphorylation, GRB2 and SOS, ras! Cell proliferation! 

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Virus acts as the ligand

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Connected to Ras-mitrogen activation, increase in activity leading to cell growth and proliferation causing hypertrophic cardiomyopathy

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hyperactive traditional pathway = increased cell growth and proliferation = cardio hypertrophy

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Noonan is due to the traditional tyrosine receptor that leads to cell growth and proliferation in the heart. This leads to progressive hypertrophic cardiomyopathy.

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Noonan syndrome

Mutations in genes controlling signaling proteins in the tyrosine kinase receptor pathways

Low set and rotated ears

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Uses both traditional and nontraditional pathways. traditional = cell growth. nontraditional = cell survivial.

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what does Metformin act on? the TKR itself, or its own receptor that activates IRS?

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BKPyV, EBV, Hep B all activate Ty-Kinase Trad. Pathway

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Metformin increases insertion of glucose receptors in the membrane to increase glucose uptake in the presence of insulin. This works to decrease plasma glucose levels

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Both traditional and nontraditional

Traditional- ligand, sos, RAS, RAF, MAP, Cell growth

Non-Traditional- Ligand, PI3K activation (by SH2 domain of p85), Akt, cell survival