Receptor cross talk is becoming widely accepted as a normal physiological method of recruiting specific signaling pathways in cells. Growth factor receptors (GFRs) that do not directly associate with or activate specific proteins can still activate the proteins indirectly by enlisting other unrelated GFRs. Roudabush et al. examine insulin-like growth factor-1 (IGF-1) receptor signaling and observe that matrix metalloproteases are involved in releasing heparan-bound EGF to activate the EGF receptor (EGFR). IGF-1-mediated Shc activation in Cos-7 cells occurred through the EGFR pathway, leading to the activation of the MAPKs Erk1 and Erk2, and, subsequently, cell proliferation. However, IGF-1 directly activated insulin receptor substrate-1 (IRS-1) and the PI3K/Akt anti-apoptotic pathway. Thus, the anti-apoptotic pathway is activated independent of EGFR stimulation. Thus it may be possible to design clinically useful drugs to selectively abrogate adverse signals in the anti-apoptotic or proliferative networks activated directly or indirectly by IGF-1. An STKE perspective by Graham Carpenter discusses the role of EGF cross talk in cellular processes.
Roudabush, F.L., Pierce, K.L., Maudsley, S., Khan, K.D., and Luttrell, L.M. (2000) Transactivation of the EGF receptor mediates IGF-1-stimulated Shc phosphorylation and ERK1/2 activation in COS-7 cells. J. Biol. Chem. 275: 22583-22589. [Abstract] [Full Text]