28.08.2019
 General Signaling Principles Composition

Outline remarks:

1 . Address - Basic signaling concepts Geraint Thomas

Introduction

Failure in cell signaling impacts the normal cellular homeostasis and then can ends in diseases. (According to OMIM between 250-2500 diseases happen to be related to innate changes elizabeth. g. IBD, Huntington, etc)

Signals stimulate transitions by state you to state installment payments on your

Even to get staying with your life cells require constant signaling.

Characteristics of a signal/change:

-- Perturbation by steady express

- Reproducible

- Handled

- Manipulated

Stimulus

Steroid hormones will be lipophilic and can therefore dissipate across sang membranes; that they form signaling complexes with proteins

A signal binds a surface receptor ( inauguration ? introduction of conformational change in the intracellular site of the radio ( transduction and exorbitance of the signal via downstream partners either linear or via network

Upon debut ? initiation ? inauguration ? introduction cells may start making signaling molecules that work either in an autocrine (same cell (type)) fashion or stuck in a job paracrine (other cells) vogue.

Adhesion elements can also stimulate signaling; if the cell can be attached or not.

Signaling requires:

-- Coordination

- Control in space

-- Control of period ( Space and temporary control):

o When?

u Where?

to For how much time?

Position – concentration – duration – sequence

Samples of stimuli: bodily hormones, neurotransmitters, ions, lipids, Gfs, odorants, cytokines, photons, different cells etc…

Mediators have diverse houses: EM radiation, solubility, size, cleavage sites etc…

Cellular material can perception damage in nearby cells for example by release of ADP coming from injured skin cells

Examples for signaling molecules:

Neurotransmitters: Acetylcholine

Hormones: LUKE WEIL, peptides, fatty acids

Cytokines: TNF alpha (3x 185AA, 20kd)

TGF beta four hundred AA

GM-CSF

Receptors

There is absolutely no pattern between signals, will there be one among receptors?

Different receptor types:

- Ion programs (voltage and ligand dependend, intracellular downstream) - 7-TM receptors (membrane spanning proteins)

- Oligomerising/oligomerised: growth factors

- Intracellular: steroid receptors, nuclear receptors, transcription elements Good news:

Receptors are extremely delicate:

в†ђ The physiological response competition is remaining (black line) to the filled receptor shape (green curve), implying that many receptors are still unoccupied whilst signaling is occurring. However , this is certainly enough to result in an enormous response.

A standard concentration to get a signal molecule is 10-10 M ( 6x1013 body hormone particles/liter Cell diameter is about 12 Вµm ( sixty hormone debris per cellular is enough to induce signaling

Good news (2):

Many pain have comparable structures

Case: 7-transmembrane spanning receptors (7-TM receptors) ( 1000 family genes out of 25000 family genes ( makes 4% of molecules which may have similarities while using 7-TM radio

Bad news:

Comparable receptors may have different components and downstream signaling, this will make them extremely complex to examine.

Positive pathways

Protein kinases: transfer of phosphate groups to protein

4 SOCIAL MEDIA PACKAGE can be phosphorylated: Serine, Threonine, Tyrosine, Histidine These AA have a hydroxyl group, which can recognize a phosphate (reverse: & water molecule). Binding of signal ( dimerization of receptors ( autophosphorylation by simply kinase site ( binding of companions ( ALTURA activated ( binds RAF ( phosphorylation of MEK

Signal cascades allow exponential amplification of signals plus more complex (and thus specific) networks

Paths are conserved over evolutionary time

Feedback amplification: self-reinforcing signaling (no matter where you start in the cascade the actual result will be the same)

Switching on/off

- GTP-binding proteins:

o Binding of GTP ( active

um Binding of GDP ( inactive

-- GAP: GTPase activating necessary protein

- A few G-proteins include internal clocks to...