Tuesday, February 26, 2013

Types of Receptors - Part 4

As we have seen in the previous post that the majority of the receptors are enzyme linked that stimulate the protein-tyrosine phosphorylation. Here, in this last post regarding the types of receptors, we will discuss about the other types of receptors that are associated with some other enzymatic activities. These are: protein tyrosine phosphatases, protein serine/threonine kinases and guanylyl cyclases. Lets understand briefly about each of these classes one by one below.

Protein Tyrosine Phosphatases:
Here, the name suggests the function i.e; phosphatases which is to remove phosphate group from phosphotyrosine residues. Thus, these receptors play a role opposite to that of protein tyrosine kinases thereby counterbalancing the kinases (just to recall, the kinases, add phosphate groups to the tyrosine residues). In some cases, the protein tyrosine phosphatases play a negative role in cell signaling pathways by stopping the signals which were initiated by protein-tyrosine phosphorylation. Whereas in some cases, the protein tyrosine phosphatases play a positive role in cell signaling by their enzymatic activities.

Serine/Threonine Kinases:
The receptors for some polypeptides phosphorylates serine or threonine residues instead of tyrosine residues on their substrate molecules. An example of such receptor is Transforming Growth Factor-β (abbreviated as TGF-β) which falls under this class of receptors i.e.; serine/threonine receptors. TGF-β is a family of growth factors which is involved in the control of proliferation and differentiation of various cell types. When the ligand binds, there is an association of two different types of polypeptides (both of which are encoded by different TGF-β receptor family) and hence forms the heterodimers. Here, one of the receptor kinases phosphorylates another one. This activated TGF-β receptors then phosphorylates another group of transcription factors called Smads, which then translocates to nucleus and causes the expression of targeted genes. The entire TGF-β signaling will be explained in the further post.

Guanylyl Cyclases:
Another class of receptors is guanylyl cyclases. Guanylyl cyclases have the cytosolic domain which catalyzes the formation of cyclic GMP. As we have seen earlier, that the signaling molecule, nitric oxide, also stimulates the guanylyl cyclase. However, the target of NO is intracellular enzyme as against the transmembrane receptor.
The receptor guanylyl cyclases have extracellular domain that binds the ligand, a single transmembrane α-helix and a cytosolic domain which has the catalytic activity. Thus, when the ligand binds at the extracellular domain, cyclase activity is stimulated which results in the formation of cyclic GMP - a second messenger.

So, finally, her we finish almost all the classes of receptors. Now, from the next post, we will proceed to the pathways of intracellular signal transduction.