Semnalizarea celularaCurs 6

Cell SignalingCelulele primesc si trimit informatii (semnale) Celulele simt si raspund schimbarilor din mediu deciSemnalele provin din interiorul celulei, de la alte celule sau din mediu

Generic Signaling PathwaySignalReceptor (sensor)

Transduction Cascade

OutputSomethinghappensoutsideinside (cytosol)

Raspunsul la semnalizarea celularaExprimarea genelor este modificata la nivelul transcrierii, a procesarii ARN sau a translatieiModificarea activitatii enzimaticeInteractiile proteina-proteina sunt induse sau inhibateSe schimba localizarea unor proteine sau a altor componenete celulareModificari biochimice

Raspunsul la semnalizarea celularaCelula:Se divide sau se inceteaza diviziuneaSe diferentiazaSe sinucide sau omoara pe cinevaSe misca sau se opreste Isi modifica metabolismulIgnora semnalulModificari fiziologice

Natura semnalului

Peptide - insulina, glucagon...ProteineDerivati din aac - histaminaBiomolecule mici - ATPSteroizi, Gaze - (NO)FotoniADN degradat

Cell respond to external signals

= A signaling molecule binds to a receptor protein, causing to change shape

= transduction: cascades of molecular interactions = Response: signaling leads to regulation of transcription or cytoplasmatic activities = signal transduction pathways

Signaling cascades have many stepsPast:EnumeratecomponentsNow: Modules Circuits/ Design Logic Cross-talk Specificity

Signaling molecules operate over various distances in animals-extracellular signaling can occur over:1. large distances or endocrine signaling signaling molecules are called hormones- act on target cells distant from their site of synthesis-usually carried through the bloodstream2. short distances or paracrine signaling affects target cells within proximityto the cell that synthesized the molecule-usually mediated by neurotransmitters and some growthfactors

Steroid Hormone Signaling PathwaySignal (steroid)

Receptor (txn factor)

Steroid Hormone Signaling PathwayOutput gene expression cell physiology

Adrenaline signalingSignal: Adrenaline (epinephrine)Secreted by adrenal gland

Receptor: b-adrenergic receptor

Response:Breakdown of glycogen to glucose to provide energy for fight-or-flight

Insulin signalingSignal: insulinSecreted by b cells of pancreasReceptor: a receptor kinaseResponse:Sugar is taken up from bloodstream into cellsDiabetes - type 1, type 2

Growth factor signaling

The growth of multicellular organisms is regulated by more than just nutrient availabilityNUTRIENTSunicellulareukaryotemulticellulareukaryote

Cells in multicellular eukaryotes require permission signals from growth factorsNUTRIENTS

Disregulation of growth factor signal transduction leads to cancerNUTRIENTScellulartransformation

Some growth factorsEGF - epidermal growth factorFGF - fibroblast growth factorNGF - nerve growth factorPDGF - platelet-derived growth factorInsulin-like GF

All of these bind to a class of receptors known as Receptor Kinases

Receptors with enzymatic activity

Protein kinases and phosphatases- Add/remove phosphates to/from proteins- Involved in all signaling from cell surface receptors, and in most other signaling too

Protein Kinase ReactionSubstrate

Phosphorylation of protein substratesProtein Kinase ReactionProduct

Phosphorylation can flip a protein from active to inactive or vis-versaATPADP

Dont worry about the all these ovals, if you know that Raf-1 activates the MAPK pathway and that MAPKs activate transcription of certain target genes, I will be happyAlso note an instance of crosstalkRas activates PI3K and you can bet that I will be talking about the PI3K pathway later b/c thats what I work on!Mammalian cells still have the ability to sense extracellular conditions and respond, but perhaps less important in the relative safety of a mutlicellular organism. However, mammalian cells are under an extra level of control . . .Energy in high energy phosphate bonds used to regulate reactions, 2 different mechanisms