Question

3. How does a steroid hormone (a type of ligand) activate gene expression?

4. What is the general role of cell surface receptor proteins in signal transduction?

Answer 1

3) Steroid Hormones like testosterone, estrogen, progesterone, etc act through effect on gene expression by binding of hormones with intracellular receptors. Steroid hormones are lipophilic in nature and can easily pass across the cell membrane.

1. Transport: After secretion the hormone is carried to the target site on serum binding protein.
2. Internalization: being lipophilic, the hormone easily diffuses through the plasma membrane.
3. Receptor-Hormone complex is formed by binding of hormone to the specific receptor inside the cell.
4. Conformational change occurs in the receptor proteins leading to activation of receptors.
5. The activated receptor hormone complex then diffuses into the nucleus and binds on the specific region of the DNA known as hormone response element which initiates gene transcription.
6. Binding of the receptor hormone complex to DNA alters the rate of transcription of mRNA.
7. The mRNA diffuse into the cytoplasm where it promotes the translation process at the ribosomes. In this way new proteins are formed which result in specific responses.

2) Cell surface receptor proteins are the receptors that are embedded in the plasma membrane of the cells. They act by binding to the signals like hormones, growth factors, nutrients, etc. They allow communication between outside the cell and inside the cell. The cell surface receptors are of three types:-

G protein coupled receptors

These are a large family of cell membrane receptors which are linked to the effector (enzyme/channel/carrier protein) through one or more GTP activated Proteins. The molecule has 7 alpha helical membrane. G proteins float in the membrane with their exposed domain lying in the cytosol and are heteromeric in composition (alpha, beta and gamma subunits). In the inactive state GDP is bound to alpha subunit at the exposed domain, activation through the receptor leads to displacement of GDP by GTP. the activated alpha subunit carrying GTP dissociates from the other two subunits and either activates or inhibits the effector. A number of G proteins are distinguished by their Alpha subunits.

Gs: adenylyl cyclase activation, calcium channel opening. (ẞ-adrenergic)

Gi: adenylyl cyclase inhibition, potassium channel opening. (GABA)

Go: calcium channel inhibition. (Dopamine)

Gq: phospholipase C activation. (Serotonin)

Three major pathways of GPCR function are: Adenylyl cyclase: cAMP pathway, Phospholipase C:IP3-DAG pathway, Channel regulation.

2) Ion channels:

Agonist binding open this channel and causes depolarization/hyperpolarization/changes in cytosolic ionic composition, etc. Example Nicotinic cholinergic, glycine, glutamate receptors.

3)Tyrosine kinase receptor

Hormone binding induces dimerization of receptor molecules, brings about conformation changes which activate the kinase to autophosphorylate tyrosine residues on each other increasing their affinity for binding substrate proteins which have SH2 domains.