MAP kinases

Mitogen-activated protein kinases were first identified by Brian Ray and Tom Sturgill as insulin-induced protein kinases. They subsequently demonstrated that these proteins were regulated by tyrosine and threonine phosphorylation via phosphorylation by MEKs. In mammalian cells there are two well characterized and highly related classical MAPKs termed Extracellular signal Regulated Kinases (ERK). A number of less related protein kinases have been identified including ERK3, ERK5 and ERK6.

The ERKs are the prototypic MAPKs and are activated by a variety of mitogenic stimuli as well as differentiation signals. MAPK activation largely requires Ras activation although activation of protein kinase C operates in a Ras-independent manner. In Drosophila, the ERK homologue is encoded by the Rolled locus (an activated allele) which has been placed downstream of Ras in the sevenless receptor kinase pathway. One of its bona fide targets in fruit flies is Drosophila Jun.

ERKs are inactivated by dephosphorylation by specific protein phosphatases such as MKP1 (CL100) and PAC1. Downstream substrates include Elk1, phospholipase A2 and p90Rsk1 (another protein kinase).

Two additional protein kinase families that are induced by stresses but not mitogens have recently been identified: the SAPKs and p38 MAPK. Like the ERKs, these stress-induced protein kinases are regulated by tyrosine and threonine phosphorylation.

One discriminator is the sequence around the activating phosphorylation sites:

• MAPK: Thr-Glu-Tyr
• SAPK: Thr-Pro-Tyr
• p38: Thr-Gly-Tyr (also ERK6/SAPK3)

These kinases are all targetted by distinct upstream enzymes (MEK1/2, SEK1 and MKK3/6).
 

We're not directly working on ERKs and so are largely relying on published data from others for this page. If you do work on ERKs and would like to contribute information to this map, let us know and we'll show you how.