• cancer

The human gene MAPK1 (mitogen-activated protein kinase 1, also known as ERK2) plays a key role in the MAPK/ERK kinase cascade and has been associated with multiple cancers. There is a single high-scoring ortholog is Drosophila, rolled (Dmel\rl), for which an extensive number of mutations, including classical amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\rl is also orthologous to the human gene MAPK3.

The human MAPK1 gene has not been introduced into flies. Several UAS constructs of the wild-type human Hsap\MAPK3 gene have been introduced into flies as part of a large-scale study of human synaptic genes; this gene may be implicated in susceptibility to autism (see FBhh0000842).

Several studies in Drosophila have assessed the activity, interactions and phenotypic impact of a mutation in Dmel\rl analogous to the most frequent pathogenic variant found in cancers, MAPK1:p.Glu322Lys . The effects of additional mutations predicted to be constitutively active have also been assessed (analogous to MAPK1:p.Asp321Asn and MAPK1:p.Arg67Ile ); these variants are predicted to be pathogenic. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): E335K in the fly rl gene (corresponds to E322K in the human MAPK1 gene); D334N in the fly rl gene (corresponds to D321N in the human MAPK1 gene); R80S in the fly rl gene (corresponds to R67I in the human MAPK1 gene and to R84H in the human MAPK3 gene). Many genetic and physical interactions have been described for Dmel\rl; see below and in the rl gene report.

[updated Feb. 2020 by FlyBase; FBrf0222196]