Enzyme-linked receptors

Numerous receptors have intrinsic or tightly related enzyme activity.  On the binding of ligand to their extracellular face such receptors undergo a conformational modify and activate an enzyme activity.  In  case  of  the  insulin receptor  that  is  a complex  of  two  α- and  two  β-subunits  held  together  through disulfide bonds the polypeptide hormone insulin the ligand binds to the extracellular face of the α-subunits. The receptor then undergoes a conformational modify leading to the autophosphorylation of the

                      Figure:  Signal transduction through an enzyme-linked receptor such as the insulin receptor.

cytosolic domain of the β-subunit.  By the Specifically hydroxyl groups in the side chains of certain tyrosine residues are phosphorylated with ATP being the phosphate donor.  Phosphorylated   receptor  is  then  identify  through  other proteins   in  the  cytosol   which  in  turn  modulate   several   intracellular   events permitting  the  cell  to  respond  to  the  hormone  appropriately.  Additionally, β-subunit can straight phosphorylate other goal proteins within the cell.

The insulin  receptor  is an instance  of a receptor  tyrosine  kinase,  although  the transforming  growth  factor TGF-β  family  of  receptors  have  serine or threonine kinase activity in their cytosolic domain. Another receptors with strongly related enzyme activity involved several cytokine receptors which bind interferons and growth hormone some interleukins and other cytokines.  For  several  ligand  binding,  enzyme- linked  receptors,   induces  the  oligomerization the formation   of dimers   or  higher   oligomers and  it  is  this  rearrangement   of  the  cytosolic domains  which enables the neighboring  kinase domains  of the receptor chains to cross-phosphorylate every other in the procedure of autophosphorylation.

Some enzyme-linked receptors as well as other receptors interact with scaffold proteins inside the cell that organize groups of proteins into signaling complexes. The  proteins  within  these  signaling  complexes  assemble by the interactions of a variety of highly conserved and small binding domains like  as  the  (Src  homology  2) SH2 domains and PTB phosphotyrosine-binding domains  which bind to phosphorylated  tyrosine residues, SH3 (Src homology  3) domains which bind to short proline-rich amino acid sequences and pleckstrin homology (PH) domains which bind to the headgroups  of inositol phospho- lipids  which  have  been  additional   phosphorylated   through  phosphatidylinositol 3-kinase PI 3-kinase.  Many scaffold proteins contain multiple PDZ domains, each of that binds to a specific motif on a receptor or signaling protein.  By the binding of these scaffold proteins to the activated receptor may help to relay the signal onward or may decrease the signaling procedures giving negative feed- back.

Figure: A hypothetical signaling complex. Binding of ligand to the extracellular face of the cell surface receptor results in phosphorylation of a tyrosine residue in its cytosolic domain. The phosphorylated tyrosine residue is recognized by an SH2 domain in the adaptor protein. Elsewhere in the adaptor protein is an SH3 domain that binds to a proline-rich sequence (PPP) in another signaling protein, such that the signal is relayed into the cell.

Some cell surface receptors needs tyrosine phosphorylation for their activity and still lack a tyrosine kinase domain. That receptors act by cytoplasmic tyrosine  kinases or  nonreceptor  tyrosine  kinases  that  relates  with  the receptor  and phosphorylate  several goal proteins.  The biggest family of cytoplasmic  tyrosine  kinases  is the Src family  which involves  Src, Yes, Fyn and Lck, that  all  contain  SH3  and  SH2  domains  and  are  situated  on  the  cytoplasmic surface of the plasma membrane.