The two predominant isoforms of the extracellular signal regulated kinases are ERK1 and ERK2 (also known as MAPK3 and MAPK1, respectively). These are often considered to be functionally redundant and any differences between the signalling pathways mediated by each of the isoforms have been attributed to their different expression levels. On page , Jim Norman and colleagues now challenge this view by dissecting a specific role for ERK2 in tumour cell migration. Knockdown of the gene encoding ERK2, but not ERK1, with isoform-specific siRNAs results in impaired invasion of breast cancer cells into Matrigel and reduces migration rates on a cell-derived matrix. This effect is rescued by the ectopic expression of ERK2 but not by an equivalent increase in ERK1 expression levels. In addition, the authors identify 27 genes whose expression is specifically controlled by the ERK2 isoform. Two of these genes encode liprin-β2 and the small GTPase Rab17, both of which are upregulated in the absence of ERK2 (but not ERK1). Furthermore, decreasing the expression levels of these proteins promotes invasion of three cancer cell lines into Matrigel, whereas overexpression of either protein impairs cell motility. The authors conclude that ERK2 – but not ERK1 – drives tumour cell motility and invasion by suppressing the gene expression of Rab17 and liprin-β2.
