A functional Jak2 tyrosine kinase domain is essential for mouse development.
Jak2 is a member of the Janus family of tyrosine kinases and is involved in cytokine signaling. As a part of a study to determine biological functions of Jak2, we used molecular modeling to identify W1038 as a residue that is critical for tyrosine kinase function. Mutation of W1038, in tandem with E1046, generates a dominant-negative form of the Jak2 protein. Mice that were engineered to express two copies of this dominant-negative Jak2 protein died in utero. Additionally, heterozygous mice expressing Jak2 with kinase activity that is moderately reduced when compared to wild-type activity appear phenotypically normal. Collectively, these data suggest that Jak2 kinase activity is essential for normal mammalian development.
Frenzel
Kristen
K
Department of Pathology, Emory University, Atlanta, GA 30322, USA. kfrenze@emory.edu
Wallace
Tiffany A
TA
McDoom
Issam
I
Xiao
Hong D
HD
Capecchi
Mario R
MR
Bernstein
Kenneth E
KE
Sayeski
Peter P
PP
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D019281:Dimerization; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D053614:Janus Kinase 2; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2