Mitogens

Mitogens such as polypeptide growth factors (PDGF, CSF-1, IGF-1, etc) as well as insulin, PMA, potently activate the ERK family of MAPKs. Most of these agents exhibit very weak (or no) induction of the SAPK and p38 kinases in most cell types. Epidermal growth factor can induce all three pathways, although the potency is variable.

Ras clearly plays a role in ERK activation. However, its function in the activation of SAPK and p38 is less clear. Many agonists of these pathways act in a Ras-independent manner. For a recent review on this topic, see:

• Lim, L., Manser, E., Leung, T. and Hall, C. (1996) Regulation of phosphorylation pathways by p21 GTPases. Eur. J. Biochem. 242, 171.
• See also: Kawasaki, et al. (1996) Ras-dependent and Ras-independent activation pathways for the stress-activated-protein-kinase cascade. Eur. J. Biochem. 241, 315.