Question

Suppose that antibody is prepared against the extracellular portion of a particular hormone receptor known to have intracellular tyrosine kinase activity, and known to carry out autophosphorylation of its tyrosine kinase. Suppose further that addition of this antibody to target cells elicits intracellular responses similar to those obtained by addition of hormone itself. Propose a mechanism by which addition of antibody may mimic the effects of adding hormone. (Hint: Fab fragments do not elicit the hormone-like response.)

Answer 1

We know that a receptor tyrosine kinase is active in its dimerized form. When a hormone binds to a receptor, it induces receptor dimerization. This leads to activation of its tyrosine kinase domain to carry out autophosphorylation. This leads to a signalling cascade in the cell leading to various effects.

It is given that antibody is prepared against the extracellular portion of the receptor. Also the Fab fragments do not elicit the hormone-like response.

We can propose a mechanism that since an antibody contains two Fab fragments, it can bind to two receptor molecules simultaneously thereby inducing dimerization of receptors. This receptor dimerization can then lead to activation of this receptor and activate the signalling cascade like that of hormone.