FKHR Background Information The transcription factor forkhead in rhabdomyosarcoma (FKHR), which is inhibited by insulin and IGF-1, enhances transcription. FKHR has been implicated in alveolar rhabdomyosarcoma, a soft tissue tumor wherein a chromosomal translocation [t(2;12)(q35;q14)] occurs between the FKHR and PAX3 genes, resulting in a novel chimeric protein with abnormal levels of expression. FKHR becomes phosphorylated at Ser 319, Ser 256 and Thr 256 by Protein kinase B (PKB) in a phosphoinsoditide 3-(PI3) kinase/Akt dependent pathway, resulting in the inactivation and subsequent nuclear exit of FKHR. In addition, FKHR becomes phosphorylated at Ser 329, also resulting in decreased FKHR activity and diminished nuclear FKHR concentration. However, phosphorylation of FKHR at Ser 329 is not mediated by a PI3-kinase-dependent pathway, but by an alternate mechanism. Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A), which co-localizes to the same region of the nucleus as FKHR, specifically phosphorylates FKHR at Ser 329 in rabbit skeletal muscle.
