Kinase Family DMPK

Kinase Classification: Group AGC: Family DMPK

DMPK kinases have 3 subfamilies, ROCK, GEK, and CRIK, that mediate signaling from small GTPases to cytoskeletal and related functions.

Subfamily ROCK

Rho-associated protein kinases that are activated by Rho GTPases and have roles in the actin cytoskeleton, motility and adhesion, proliferation, and apoptosis. Two human genes (ROCK1, ROCK2) with single homologs in most invertebrates and down to sponges.

Subfamily GEK

Includes the mammalian genes DMPK1 and DMPK2, MRCKa and MRCKb, and single homologs in invertebrates, sponge and fungi. MRCKs are regulated by the cdc42 small GTPase, while DMPKs are rho-activated

Subfamily CRIK

A single gene in most metazoans, absent from sponges. Functions in cytokinesis (in both Drosophila and mammals) and during neuronal development (mammals).

Evolution

GEK is found in fungi and animals, while ROCK and CRIK are animal-specific kinases

Domain Structure

All DMPK kinases are long proteins (~1500-2000 AA) with an N-terminal kinase domain and varied other domains including TMF (DNA binding), PH (lipid binding), CNH, C1, and citron domains