Diagram illustrating Functional JAK STAT PathwayThis “JAK STAT” pathway appears to be ubiquitous amongst vertebrates

Diagram illustrating Functional JAK STAT PathwayThis “JAK STAT” pathway appears to be ubiquitous amongst vertebrates. Following ligand binding the activated JAK2 protein catalyses tyrosine phosphorylation in the cytoplasmic domain of the receptor and also leads to phospharylation of the Signal Transducers and Activators of Transcription (STATS).Phosphorylation of STAT leads to dimerisation via conserved Src homology 2 (SH2) domains. Translocation of these dimers to the nucleus then occurs facilitated via Nucleoprotein Interactor 1 (NPI-1). Subsequent regulation of gene expression following interaction with DNA response elements occurs. This leads to a transcriptional response. There is also interaction with the RAS/MAPK, Pl-3 K and Akt downstream pathways.Under normal conditions the enhanced gene expression is under complex negative feedback mechanisms including amongst others the production of the negative regulator Suppressors of Cytokine Signalling (SOCS).

Publication

JAK2 V617F: A Single Mutation in the Myeloproliferative Group of Disorders. (2006) Donal McLornan, et al. Ulster Med J. 2006 May;75(2):112-119. Figure: F1. All organisms Homo sapiens Drosophila melanogaster

Disease mentions