PLCγ is a very important enzyme in the pathway as it generates second messenger molecules. It is activated by the tyrosine kinase Itk which is recruited to the cell membrane by binding to Phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 is produced by the action of Phosphoinositide 3-kinase(PI-3K), which phosphorylates Phosphatidylinositol 4,5-bisphosphate (PIP2) to produce PIP3. It is not known that PI-3K is activated by the T cell receptor itself, but there is evidence that CD28, a co-stimulatory receptor providing the second signal, is able to activate PI-3K. The interaction between PLCγ, Itk and PI-3K could be the point in the pathway where the first and the second signal are integrated. Only if both signals are present, PLCγ is activated.