CELL SIGNALING Receptors

1. CELL SIGNALINGReceptors

3. Cell signaling Function of the cell is regulated. Different substances (signaling molecules or first messengers) act upon the cell. Different response of the cell depends on: Type of the messenger (ligand) Capability to recognize the messenger Intracellular signals which are triggered by the receptor

4. Cell signaling: one cell sends a signal molecule (ligand) and other cell has a molecule responsible for reading an information (receptor) and is able to conduct a special reaction in answer to the signal.

5. Types of answer in cell signaling: Effects of the siganling: change of shape or movement, changes in gene expression, Combination of many signals may be responsible for: survival, division, deferentiation, death of the cell.

7. Cell response

8. AIM Activation or disactivation of various proteins � enzymes This is achieved most often by PHOSPHORYLATION Enzymes which phophorylate are called KINASES So the aim is to activate KINASES

9. CELL SIGNALING Autocrine signaling Paracrine signaling Endocrine signaling Nerve signaling

10. Types of cell siganling: Endocrine type � hormones, Autocrine type � cell sends chemical signal to itself, Paracrine type � local mediators, Neuronal type � neurotransmitters, Contact of the cells � membrane molecules

13. Endocrine signaling Hormones are carried in the blood to target cells throughout the body

14. Signaling pathsways: Receptor receives a signal and generate intracellular signaling path, That leads up to cascade reaction of many factors

15. Reaction of the intracellular factors: Change of signal in molecular form which leads up to signals transduction, Transduction- from the point of receiving of the signal to the point of answering to this signal, amplification of the signal, Spreading of the signal, Modulation of the signal.

17. Types of signaling molecules: Substances which can penetrate plasma membrane (hydrophobic signaling molecules) And activate the enzyme pathways, And react with intracellular receptors STEROIDS THYROID HORMONES Substances which have receptors in the plasma membrane.( hydrophilic signaling molecules)

18. Types of signaling molecules

19. Receptors Oragans of senses of the cell First messenger specific Translate the signal of first messenger into �cell language� which leads to its response (action � contraction, release, movement, mitosis, activation or disactivation of a metabolic pathway etc.) IN FACT THIS IS RELATED TO ACTIVALION OR DISACTIVAION OF ENZYMES MOST OFTEN BY MEANS OF PHOPHORYLATION OR ALLOSTERIC EFFECT

20. TYPES OF RECEPTORS -ION CHANNEL-LINKED -G-PROTEIN-LINKED -ENZYME-LINKED -CYTOPLASMIC AND NUCLEAR

21. Membrane receptors: Ion channels, Coupled with G protein, Coupled with an enzyme.

22. Ion channels: Abudant in nervous system and in muscle cells, They transform chemical signals into electrical signal by opening the channels (effux or infflux of the ions),

24. Ion channel

25. Ion channel linked receptor

26. Receptor coupled with enzymes: Transmembrane proteins bounded up with the enzymes, Coupled with thyrosine kinases or seryne-threonine kinases, Are responsible for information integration which leads up to complex control of the cell behavior.

27. Insulin and IGF1 receptor Composed of 4 subunits-2 alfa and 2 beta glycoproteins

30. Receptors coupled with G protein: Receptor is connected to G protein complex in the cytosol, Activated G protein may regulate the ion channels, some of them can activate membrane enzymes � adenylan cyclase (cAMP) or phospholipase C (IP3, diacylglicerol)?

33. Primary messengers: Hormones, Humoral factors � histamine, Growth factors � IGF, EGF, NGF, Neurotransmitters � dopamine, Ach, Limfokines � IL, Drugs.

34. Secondary messengers There are three basic types of secondary messenger molecules: Hydrophobic molecules: water-insoluble molecules, like diacylglycerol, IP3, and phosphatidylinositols, which are membrane-associated and diffuse from the plasma membrane into the juxtamembrane space where they can reach and regulate membrane-associated effector proteins Hydrophilic molecules: water-soluble molecules, like cAMP, cGMP, and Ca2+, that are located within the cytosol Gases: nitric oxide (NO) and carbon monoxide (CO), which can diffuse both through cytosol and across cellular membranes.

35. Second messengers: Ions - Ca 2+ IP3, diacyloglicerol, cAMP, cGMP,

38. G protein coupled receptor - cAMP

39. IP3,DAG Second Messengers: IP3 and DAG Inositol triphosphate (IP3) and diacylglycerol (DAG) are important second messengers. Their formation begins with the binding of an extracellular regulatory molecule to a membrane receptor that activates a trimeric G protein. The alpha subunit of this G protein then activates phospholipase C, which acts on a membrane phospholipid. Acting on a membrane phospholipid, phospholipase C cleaves off IP3, which is a small polar molecule. Remaining in the membrane is the DAG, which consists of glycerol and two fatty acids The IP3 diffuses to the endoplasmic reticulum, which stores Ca++. The IP3 binds to and opens a ligand gated ion channel that allows Ca++ to move out into the cytosol, where the Ca++ activates various cellular processes. This is discussed further under calmodulin page. (Note that in muscle, the Ca++ is stored in the sarcoplasmic reticulum.) Meanwhile, the DAG in the membrane activates protein kinase C, which in turn activates proteins inside the cell by phosphorylation.

40. IP3, DAG

41. Types of signaling molecules: Substances which can penetrate plasma membrane (hydrophobic signaling molecules) And activate the enzyme pathways, And react with intracellular receptors STEROIDS THYROID HORMONES Substances which have receptors in the plasma membrane.( hydrophilic signaling molecules)

42. NO ( nitro oxide): Is a local mediator, Can penetrate the plasma membrane, Activates the production of the cGMP- intracellular mediator, Leads up to dilation of the smooth muscle cells of the blood vessels (increases the lumen and blood flow in these vessels)?

44. Steroid hormones: Easily passing through the plasma membrane, They bound up with the receptor in the cytosol and nucleus, Bounding to the receptor leads up to change of its conformation (activation) and initiation or inhibition of the transcription of the genes.

48. Cushing syndrome