Membrane based classification of signalling pathways

MEMBRANE BASED EXTRACELLULAR AND CYTOSOLIC OR INTRACELLULAR RECEPTORS AND THEIR COMPARISON WITH RESPECT TO SIGNALING

Presented by Ajit kumar dansena M.Sc Life Sciences Central university of gujarat

TYPES OF RECEPTOR

RECEPTOR

EXTRACELLULAR

INTRACELLULAR

G-PROTEIN COUPLED RECEPTOR

Enzyme linked receptor

Ion channelled receptor.

Cytosolic receptor

Nuclear receptor

EXTRACELLULAR RECEPTOR Cell surface receptors (membrane

receptors, transmembrane receptors) are specialized integral membrane proteins that take part in communication between the cell and the extracellular environment.

Extracellular signaling molecule ( hormone , neurotransmitter , cytokines , growth factor and cell recognition molecule ) attach to receptor , trigger the changes in function of the cell ,relay the signal through different intracellular proteins- the process is called signal transduction.

Cont….. Extracellular receptors having 3 type of

domain – 1  Extracellular domain

2  Transmembrane domain

3  Intracellular domain

G Protein coupled receptor

G-Protein coupled receptor also name known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, and G protein–linked receptors (GPLR).

GPCRs associate with trimeric G-proteins , consisting of an alpha, beta, and gamma subunits .

G-alpha bound to GTP is active, and can diffuse along the membrane surface to activate target proteins, often enzymes that generate second messengers.

Enzyme linked receptors

Catalytic receptor. Integral membrane protein. Extracellular ligand binding domain. Intracellular enzymatic domain and

it shows enzymatic activity.

Single transmembrane domain.

Classification of enzyme linked

There are five main types of enzyme-linked receptors:

Receptor Tyrosine Kinase (RTK)

Receptor Serine/ Threonine Kinase

Receptor Guanylyl Cyclases

Tyrosine-Kinase Associated Receptors

Receptor Tyrosine Phosphatases

receptor

Tyrosine kinase receptor This family include the receptor for most

polypeptide growth factor . First protein-tyrosin kinase was discover during

studies of oncogenic protein of Rous sarcoma virus. steps -: ligand receptor dimerization forming cross link

dimer in enzymatic domain activation cross phsphorylation binding of protein (SH2)

signal transduction regulation of gene transcription

Cont….. Major role of tyrosin kinase is inhibitor in

cancer therapy

Receptor Serine/Threonine Kinase Phosphorylates specific serines or

threonines on themselves. Phosphorylates latent gene regulatory

proteins with which they are associated. Eg:-The Smad-dependent signaling

pathway activated by TGFβ.

Receptor Guanylyl Cyclase Signalling cascade that is activated by low

intracellular calcium levels and inhibited by high intracellular calcium levels. In response to calcium levels.

In response to ca+ levels guanylyl cyclase synthesizes cGMP from GTP.

GMP acts as a small intracellular mediator in much the same way as cAMP.

Cont….. Types of guanylate cylase-:(1) membrane- bound (type-1 guanylate

cyclase coupled receptor)(2) soluble (type-2 soluble guanylyl

cyclase)

Tyrosine-Kinase Associated Receptors

Lack tyrosine kinase domain.

Depend on tyrosine phosphorylation.

Cytoplasmic tyrosine kinase.

eg:- JAK-STAT pathway .

Jak stat signalling pathway

Receptor Tyrosine Phosphatases protein tyrosine phosphatases (PTPs) are involved in

the regulation of key cellular processes by controlling the phosphorylation levels of diverse effectors.

 receptor-like protein tyrosine phosphatases (RPTPs) are involved in important developmental processes, particularly in the formation of the nervous system.

Receptor-like protein tyrosine phosphatases (RPTPs) continue to emerge as important signalling molecules in axons and their growth cones.

Cont…. Recent findings show that Drosophila

RPTPs play key roles in guiding retinal axons and in preventing midline crossing of longitudinal axons.

Vertebrate RPTPs are now implicated in controlling axon outgrowth, and preliminary evidence suggests that they too may influence axon guidance.

Ligand gated ion channel  LGICs are transmembrane ion channel , which open to allow ion such

as ( Na+, K+, Ca+ or Cl-) .

To pass through the membrane in response to the binding of a chemical messenger( ligand) such as neurotransmitter

Domain :- 1 transmembrane domain 2 extracellular domain

Intracellular receptors Intracellular receptors are present inside

cell .  intracellular receptors include thyroid

and steroid hormones. Class-: cytosolic and nuclear receptors Intracellular receptors that can be found

in the cytoplasm or in the nucleus . They bind to extracellular signaling

molecules that migrate through or are transported across the CELL MEMBRANE. 

Cont…..  Many members of this class of receptors

occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation.

Ex-: NO Pathway Ligand -: Nitric oxide (NO) Receptor -: cytosolic guanylyl cyclase signal transduction -: generation of

cGMP

Nuclear receptorEX-: Steroid , Thyroid hormone etc .

Compare internal receptors with cell- surface receptor

Intracellular receptors are located in the cytoplasm of the cell and are activated by hydrophobic ligand molecules  that can pass through the plasma membrane.

Cell-surface receptors bind to an external ligand molecule and convert an extracellular signal into an intracellular signal.

Intracellular receptor is having NLS system. Extracellular receptor is having three domain . Hinge reason is present in intracellular receptor. Intracellular receptor is having HSP .

Refrance Molecular Biology of the Cell- Bruce

Alberts The Cell – Cooper and Hausman Principle of biochemistry – Lehninzer WIKIPEDIA http://physrev.physiology.org/content/87

/3/905