Activation of Protein kinase C, alpha type by Diacylglycerol PathwayStep2033 Activated PKC-alpha can activate MMP3 GRB2:SOS1 binds to HBEGF:p-Y-EGFR Mature HBEGF binds to EGFR, triggering dimerisation and autophosphorylation of the receptor Active MMP3 can cleave pro-HBEGF to form active HBEGF SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated) PathwayStep5825 PathwayStep5824 PathwayStep5827 PathwayStep5826 PathwayStep5828 EGFR Transactivation by Gastrin Authored: Jassal, B, Tripathi, S, 2012-04-04 Edited: Jassal, B, Tripathi, S, 2012-04-04 Gastrin, through the action of diacylglycerol produced from downstream G alpha (q) events, transactivates EGFR via a PKC-mediated pathway by activation of MMP3 (Matrix Metalloproteinase 3) which allows formation of mature HBEGF (heparin-binding epidermal growth factor) by cleaving pro-HBEGF. Mature HBEGF is then free to bind the EGFR, resulting in EGFR activation (Dufresne et al. 2006, Liebmann 2011). Pubmed16816139 Pubmed20398727 Reactome Database ID Release 432179392 Reactome, http://www.reactome.org ReactomeREACT_121096 Reviewed: D'Eustachio, P, 2012-04-23