Signal transduction and hormone receptor complex

signal

• A signal is a message that can influence the location of proteins in the cell and can affect general processes such as protein synthesis, cell growth and replication, perhaps through effects on gene expression.

• Intracellular signaling describes the mechanism by which one cell sends the messages to change the function of another cell.

Some signals that cell respond

• Antigens

• Growth factors

• Hormones

• Light

• Mechanical touch

• Neurotransmitter

• Nutrients

• odorents

ligand

• A ligand is any molecule that binds a receptor protein.

• Agonist

• Ligand that on binding activates signal transduction.

• Antagonist

• It prevents signal transduction

receptors

• Receptors may be protein in nature.

• Receptors interact with effector protein.

• There are two major classes of receptors

• Intracellular receptor

• Cell surface receptors

receptors

• G-Protein coupled receptor

• Receptor tyrosine kinase

• Receptor guanylyl cyclase

• Gated ion channel

• Adhesion receptor

• Nuclear receptor

receptors

• Several classes of peptide hormone are defined.

• Insulin receptor is a heterotetramer composed of two copies of two different subunits.alpha2 and beta 2.

• They are linked by disulphide bridges.

• Alpha subunit binds insulin.

• Membrane spanning beta subunit traduce the signal through the tyrosine kinase domain located in the cytoplasmic portion of this polypeptide.

• Receptor for insulin like growth factor and epidermal growth factor are generally similar in structure to the insulin receptor.

Hepta-helical receptor

• Poly peptide hormone and catecholamine receptors ,which transduce the signal by altering the rate of production cAMP through G-protein are characterized by the presence of seven domains that span the plasma membrane.

• Protein kinase activation and generation of cAMP is a down stream action of this class of hormone.

Specificity and selectivity of hormone receptors

Hormonal involvement in response to a stimulus

Steps in signal transduction

• Binding of extracellular agonist.

• Change in intrinsic energy.

• Receptors counteract with effector protein.

Signal generation

• The lipophilic group 1 hormones diffuse through the plasma membrane of all cells but only encounter their specific high affinity receptor in target cells. These receptors can be located in the cytoplasm or in the nucleus of the target cell. The hormone receptor complex undergoes an activation reaction. Receptor activation occurs by two mechanisms.

• Glucocorticoid diffuses across the plasma membrane and encounter their cognate receptor in the cytoplasm of target cell.

• Ligand receptor binding results in conformational change in the receptor leading to dissociation of heat shock proteins90.

• The activated receptor moves into the nucleus and binds with high affinity to a specific DNA sequence called hormone response element.

• Certain hormones such as thyroid hormone and retinoid diffuse from the extracellular fluid across the plasma membrane and go directly into the nucleus.

Signal generation

Group 2 hormone

• Many hormone are water soluble, have no transport protein and initiate a response by binding to a receptor located in the plasma membrane.

• The mechanism is best described in terms of intracellular signal.

• These signals include cAMP etc.

G-protein coupled receptor

• Many group II hormones bind to receptor that couple to effector through a GTP binding protein.

• Receptors have seven hydrophobic domains.

• Receptors of this class which signal through guanine nucleotide bound intermediates are known as G-PROTEIN COUPLED RECEPTOR.