Chapter 16 Cell Bio

Modes of cell-cell signaling

Endocrine signaling

Paracrine signaling

Autocrine signaling

Endocrine signaling

Hormones are secreted into circulatory system and are carried far

Paracrine signaling

Molecule is released by one cell and acts on a neighboring cell

Autocrine signaling

Cell releases signal that it responds to

Characteristics of steroid hormones

Small hydrophobic

Can diffuse across plasma membrane

Synthesized from cholesterol

Major steps of glucocorticoid signaling

Glucocorticoid diffuses through plasma membrane and binds to receptor

Causes conformation change of receptor, displaces from chaperone Hsp90, exposes nuclear localization signals

Activated receptor binds to recognition site, associates with coactivator HAT

Thyroid Hormone Receptor Regulation

Receptor always attached to DNA

Hormones cause conformational change

Corepressor HDAC leaves, coactivator HAT binds

Nitric Oxide Synthesis

Neurotransmitters act on endothelial cells to stimulate NO synthesis

NO diffuses across plasma membrane, alters activity of guanylyl cyclase, stimulating cyclic GMP synthesis

cGMP induces muscle relaxation

Main groups of peptide signaling molecules

Peptide hormones

Neuropeptides

Growth factors

Basic structural unit for peptide signaling molecules

amino acids

Can peptide signaling molecules diffuse across plasma membrane?

no

Structural characteristics of G-protein coupled receptor

Carbohydrates attached near N terminus

Seven transmembrane alpha helices

Intracellular + extracellular ligand binding domain

Intracellular domain has guanine nucleotide exchange factor

Role of carbohydrates in g-protein coupled receptors

Proper folding

Hormonal activation of adenylyl cyclase by epinephrine

Epinephrine bids to receptor, induces conformational change of intracellular domain to act as a GEF

GDP exchanged for GTP on g-protein, activates it

Alpha subunit dissociates and carries signal to adenylyl cyclase

GTPase activating protein role

Hydrolysis of GTP to GDP

without GAP, g-proteins constitutively on, leading to unregulated cell division

Steps to glycogen breakdown

Epinephrine sends signal to adenylyl cyclase through g-protein

Adenylyl cyclase converts ATP to cAMP

cAMP activates protein kinase A, releasing catalytic unit

Catalytic unit activates phosphorylase kinase

Glycogen phosphorylase activated

What does cholera toxin do?

Inhibits ability of alpha subunit of g-protein to hydrolyze GTP

steps to expression of cAMP inducible genes

Catalytic unit from protein kinase A translocates to nucleus

Phosphorylates transcription factor CREB

Coactivators get recruited, gene induced

Receptor tyrosine kinase

Has c-terminal tyrosine kinase domain that will cross phosphorylate each other

Nonreceptor tyrosine kinase

Has associated nonreceptor tyrosine kinase at c-terminus

Role of RAS in ERK MAP kinase signaling

GEF exchanges GDP for GTP in Ras, activating it
activated ras starts pathway via phosphorylation
GTPase hydrolyses GTP to GDP to inactivate

Steps that lead to AKT activation

Growth factor binds to receptor, phosphorylates receptor tyrosine kinase

PI 3-kinase recruited via SH2 domain

PI 3-kinase converts PIP2 to PIP3

Akt recruited by binding to PIP3

mTOR2 and PDK1 bind to PIP3, activating Akt

TGF-b / Smad pathway activation

type II receptor phosphorylates and activates type I

Type I phosphorylates Smad protein

Activated Smads form complexes, translocate into nucleus, activate transcription

NF-kB pathway

Activated TNF recruits adaptor protein that activates lkb kinase

phosphorylation makes lkb for ubiquitination

lkb degraded by proteasome

NF-kB translocates to nuclease to activate transcription

Notch pathway

Binding of delta (signal) leads to cleavage of Notch

Notch enters nucleus, interacts with CSL transcription factor, induces gene expression