Fig. 10. Schematic representation of the signal transduction pathway utilized by cholinergic agonists and EGF in the conjunctival goblet cells. Muscarinic receptors (M2 and M3) activate G-proteins (Gαq/11), which in turn stimulate phospholipase C (PLC). PLC generates the production of the second messenger, inositol trisphosphate (IP3), which causes a rise in the concentration of intracellular Ca2+ and diacylglycerol (DAG), which activates PKC. Both pathways potentially lead to secretion. The increase in Ca2+ and activation of PKC stimulate the non-receptor tyrosine kinases Pyk2 and Src to transactivate the EGF receptor (ErbB). EGF binds to its receptor to activate its intrinsic tyrosine kinase activity. This stimulates the recruitment of the adaptor proteins Shc, Grb2, and Sos. This activates the protein kinase cascade of Ras, Raf (MAPK kinase kinase), MEK (MAPK kinase), and ultimately p42/p44 MAPK. The activation of either pathway (Ca2+/PKC or MAPK) leads to protein secretion from the conjunctival goblet cells.26