Editors' ChoiceMolecular Scaffolds

A Scaffold for Kinases

Science's STKE  28 Nov 2000:
Vol. 2000, Issue 60, pp. tw4
DOI: 10.1126/stke.2000.60.tw4

The β-arrestins were so named because they function in the desensitization of β2-adrenergic receptors. However, these proteins play other roles both in receptor endocytosis and in promoting receptor signaling. McDonald et al. now describe yet another function for these versatile proteins: β-arrestin 2 binds to the mitogen-activated protein kinase family member JNK3 (c-Jun NH2-terminal kinase 3) and to the upstream kinases MKK4 and ASK1 that act in a cascade to activate JNK3. β-Arrestin 2 appears to act as a scaffold that brings the kinases together and helps retain JNK3 in the cytosol. In cells treated with agonists of G protein-coupled receptors (GPCRs), the β-arrestin 2 protein appears to target JNK3 to endosomal vesicles. A perspective by Pouysségur provides greater detail on the mechanism of GPCR-mediated MAPK activation.

McDonald, P.H., Chow, C.-W., Miller, W.E., Laporte, S.A., Field, M.E., Lin, F.-T., Davis, R.J., and Lefkowitz, R.J. (2000) β-Arrestin 2: A receptor-regulated MAPK scaffold for the activation of JNK3. Science 290: 1574-1577. [Abstract] [Full Text]

Pouysségur, J. (2000) Signal Transduction: An arresting start for MAPK. Science 290: 1515-1518. [Full Text]