CELL SIGNALING (BIO-203) Credit Hrs 3

Course Contents Overview of cell signaling Principles of cell signaling Types of ligands and

receptors Signaling through enzyme

liked cell-surface receptors Receptor tyrosine kinases

and non-receptor tyrosine kinases

Signaling via receptor tyrosine kinases

Signaling via tyrosine kinase associated receptors

Signaling via receptor serine-/threonine kinases

Signaling through G protein linked receptors

Small GTPases G protein coupled receptors

Lipid (2nd messengers)-mediated cell signaling

Synaptic signaling ATP-signaling Purinergic (P2X and P2Y) signaling iNOS siganling Cell adhesion molecules Signaling events in acute

inflammation (native immunity) Events at the postcapillary venule Wound repair Hematopoiesis Why and how do cancer cells

become independent of extracellular signals?

Selected examples Plant cell signaling (role of growth

factors, hormones and pheromones)

Plant defense mechanism Signaling in microbes

Recommended Books Molecular Cell Biology by Lodish and co. 6th Ed Molecular Biology of the Cell by Bruce Albert and

Dennis Bray. Garland Publishing Inc, New York and London. Handbook of Cell Signaling Vol 1-3, by Ralph

Bradshaw, and Edward Dennis. Cell Signalling, by John T. Hancock, 2nd ed. Oxford

University Press. Apoptosis, Cell Signaling, and Human Diseases:

Molecular Mechanisms, Volume 2 by Rakesh Srivastava.

Cell Signaling and Growth Factors in Development: From Molecules to Organogenesis by Klaus Unsicker (Editor), Kerstin Krieglstein.

Signal Transduction by Bastien D. Gomperts. The Biochemistry of Cell Signalling by Ernst J. M.

Helmreich.

Total MarksFirst OHT 15 marksSecond OHT 15 marksFinal Exam 50 markQuizzes (2-4)10 marksAssignment/project

/presentation10 marks

Time tableWed (11:30-1:00) Thurs (11:30-1:00)

Cell Signaling (Lecture 1)

IntroductionCells can not live in an isolated environment. Prokaryotes communicate with each other,

other organisms and surrounding environment. Eukaryotes e.g yeasts, slime molds, and

protozoans mate, differentiate and respond to the environment by secreting pheromones

Cells are able to receive and process signals. Individual cells receive many signals

simultaneously, and they then integrate the information they receive into a unified action plan.

They also send out messages to other cells both near and far.

What kind of signals do cells receive?

Most cell signals are chemical in nature.Prokaryotic organisms have sensors that

detect nutrients and help them navigate toward food sources.

In multicellular organisms, growth factors, hormones, neurotransmitters, and extracellular matrix components are some of the many types of chemical signals cells use.

These substances can exert their effects locally, or they might travel over long distances.

Some cells also respond to mechanical stimuli. For example sensory cells in skin and ear.

Types of signaling moleculesSmall molecules: amino acids,

lipid derivatives, acetylcholinePeptides: ACTH, vasopressinSoluble proteins: Insulin, growth

hormones

Signaling in plants and animalsIn plants and animals, extra

cellular signaling molecules control

MetabolismGrowth and differentiation of

tissuesSynthesis and secretion of

proteinsComposition of intracellular and

extracellular fluids

General principle signaling1. Synthesis of signaling molecules by the

signaling cells2. Release of signaling molecules3. Transport of the signal to the target cell4. Detection of a signal by a specific

receptor protein present on the target cell5. A change in cellular metabolism, function

or development triggered by the receptor-signal complex

6. Removal of the signal, which often terminate the cellular response

Signaling cell

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Cellular responses due to cell signalingChanges in the activity or

function of specific enzymes and other proteins present in the cells

Changes in the amount of protein produced by a cell e.g. modification of transcription factors that stimulate or repress gene expression

Types of signaling

Autocrine Signaling Can Coordinate Decisions by Groups of Identical Cells

Cells send signals to other cells.

Cells send signals to themselves.

Cell secretes signaling molecules that can bind back to its own receptors.

It is most effective when carried out simultaneously by neighboring cells of the same type.

Thus autocrine signaling is thought to be one possible mechanism underlying the "community effect" observed in early development, where a group of identical cells can respond to a differentiation-inducing signal but a single isolated cell of the same type cannot.

Gap Junctions Allow Signaling Information to Be Shared by Neighboring Cells

Signals are passed to the neighboring cells through gap junctions.

These are specialized cell-cell junctions that can form between closely apposed plasma membranes, directly connecting the cytoplasms of the joined cells via narrow water-filled channels.

(b)(a) (c)

(d)

(c1) (c2) (c3) (c4) (c5)

The channels allow the exchange of small intracellular signaling molecules, such as Ca2+ and cyclic AMP, but not of macromolecules, such as proteins or nucleic acids.

Thus cells connected by gap junctions can communicate with each other directly without having to deal with the barrier presented by the intervening plasma membranes.

gap-junction communication helps adjacent cells of a similar type to coordinate their behavior.

It is not known, however, which particular small molecules are important as carriers of signals through gap junctions; nor has the precise function of gap-junction communication in animal development been defined.

Receptor protein exhibit ligand binding effectReceptor present on Plasma or nuclear

membrane has ligand binding sitesSignaling molecules (hormones,

pheromones or neurotransmitters) act as ligands

Confirmational change occurs in the receptor that initiate a sequence of chemical reactions

Receptor proteins are specific for each horomone

Different cells have different sets of receptor for the same ligand and each of which induces a different response

Different cells respond in a variety of way to the same ligand (e.g. acetylcholine)

Different ligands can induce the same cellular response in some cells (glucagon/epinephrine)

In most receptor-ligand system, the ligand do not have any function except to bind to receptor

Upon binding it changes the properties of receptor which then produce signals to the cell that a specific product is present

Target cells often degrade or modify the ligand to terminate or modify their response

Those who knowLight in the world are those, who knowGuides of mankind are those, who knowWhen looking for the road to GodAnd Prophet, ask from those, who knowThe alchemist in his researchFinds sympathy from those, who knowA desert stone will turn to goldIn company with those, who knowThose are not humans, only shellsThe empty ones, who do not know

(Rehman Baba)

Believe in yourself“Don't be satisfied with stories, how things

have gone with others. Unfold your own myth.”  Rumi

“Life is too short to waste any amount of time on wondering what other people think about you. In the first place, if they had better things going on in their lives, they wouldn't have the time to sit around and talk about you. What's important to me is not others' opinions of me, but what's important to me is my opinion of myself.”  Anonymous