Semnalizarea celulara

Curs 6

Cell Signaling
- Celulele primesc si trimit informatii (semnale) - Celulele simt si raspund schimbarilor din mediu deci Semnalele provin din interiorul celulei, de la alte celule sau din mediu

Generic Signaling Pathway

Signal Receptor (sensor)
outside inside (cytosol)

Transduction Cascade

Output

Something happens

Raspunsul la semnalizarea celulara

Modificari biochimice

Exprimarea genelor este modificata la nivelul transcrierii, a procesarii ARN sau a translatiei Modificarea activitatii enzimatice Interactiile proteina-proteina sunt induse sau inhibate Se schimba localizarea unor proteine sau a altor componenete celulare

Raspunsul la semnalizarea celulara

Modificari fiziologice

Celula:
Se divide sau se inceteaza diviziunea Se diferentiaza Se sinucide sau omoara pe cineva Se misca sau se opreste Isi modifica metabolismul Ignora semnalul

Natura semnalului
Peptide - insulina, glucagon... Proteine Derivati din aac - histamina Biomolecule mici - ATP Steroizi, Gaze - (NO) Fotoni ADN 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 steps

Past: Enumerate components

Now: 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 bloodstream 2. short distances or paracrine signaling affects target cells within proximity to the cell that synthesized the molecule -usually mediated by neurotransmitters and some growth factors

Steroid Hormone Signaling Pathway

Signal
(steroid)

Receptor
(txn factor)

Steroid Hormone Signaling Pathway

Output
gene expression cell physiology

Adrenaline signaling
Signal: Adrenaline (epinephrine)
Secreted by adrenal gland

Receptor: b-adrenergic receptor

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

Insulin signaling
Signal: insulin
Secreted by b cells of pancreas

Receptor: a receptor kinase Response:

Sugar is taken up from bloodstream into cells

Diabetes - type 1, type 2

Growth factor signaling

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

unicellular eukaryote

NUTRIENTS

NUTRIENTS multicellular eukaryote

Cells in multicellular eukaryotes require permission signals from growth factors

NUTRIENTS

NUTRIENTS

Disregulation of growth factor signal transduction leads to cancer

NUTRIENTS

NUTRIENTS cellular transformation

Some growth factors

EGF - epidermal growth factor FGF - fibroblast growth factor NGF - nerve growth factor PDGF - platelet-derived growth factor Insulin-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 Reaction

Kinase
ATP
PP P

Substrate

Phosphorylation of protein substrates

Protein Kinase Reaction

PP

Product

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

ATP

ADP