Signal Transduction Pathways Overview

Upstream

Upstream

Steps/components closest to the reception

Downstream

Steps/components closest to cell response

Multimerization

occurs when ligand binds receptor and other receptors join in a group, triggers phosphorylation of tyrosine (usually)

Tyrosine

amino acid that is usually phosphorylated in upstream molecules

Serine and Threonine

phosphorylation of amino acids is more common downstream

Kinases

Add phosphate groups to proteins

Phosphatases

Remove phosphate groups from proteins

Lipid Rafts

associated with multimerization, kinases are on the rafts and with multimerization can phosphorylate all proteins at once

SRC

protein that is phosphorylated and inactive, but removal of the phosphate and addition of another phosphate to a different part is required for full activation

Adapter Proteins

form a protein scaffold to activate or deactivate groups of proteins at once

Scalable signaling

degree of response can change based on factors such as degree of phosphorylation

Reasons for varied response in body

enzymes present, transcription factors present, scalable signaling, multiple-ligand receptor interactions required

Oxidative burst

produces large amounts of chemicals such as hypochlorous acid, peroxide, superoxide radicals (used by innate cells to kill pathogens)

G-protein coupled receptor

GPCR, bound to GDP (inactive) or GTP (active)

GTP

active ligand of G-protein

GDP

inactive ligand of G-protein

Active GPCR

can travel across the plasma membrane to activate other enzymes and molecules to initiate signal cascade

7-Pass Mechanism

mechanism with GPCR trimer being split up when activated to produce 3 special functions

GPCR trimer

alpha, beta, and gamma subunits involved in 7-pass mechanism

Cγ

phospholipase, important first step in NF-KB and NFAT signaling, breaks down phosphatidyl inositol bisphosphate into inositol trisphosphate and diacylglycerol

Diacylglycerol

binds and activates protein kinase C, part of NF-KB signaling

Protein kinase C

phosphorylates IKB, part of NF-KB signaling

IKB

inhibits NF-KB, but releases it when phosphorylated

Phosphatidyl inositol bisphosphate

breaks down into soluble inositol trisphosphate and membrane-bound diacylglycerol

Inositol trisphosphate

binds intracellular calcium vesicles to release Ca2+, part of NFAT signaling

Ca2+

activates calmodulin, part of NFAT signaling

Calmodulin

activated form binds and activates calcineurin, part of NFAT signaling

Calcineurin

dephosphorylates transcription factor NFAT so it can migrate into nucleus

SOS

nucleotide exchange factor protein activated by RAM phosphorylation, binds Ras

Ras

g-protein that exchanges GDP for GTP when SOS binds to form complex that activates Raf

Ras-GTP complex

migrates and binds cytoplasmic Raf

Raf

phosphorylates MEK to activate it

MEK

phosphorylates ERK to allow it to enter nucleus

ERK

phosphorylates Fos, one of the components for transcription factor AP-1

Fos

one of the components of AP-1