Jak Isoform Antibody

The four JAK family members, Jak1, Jak2, Jak3 and Tyk2, range in size from 120 to 140 kDa, and except for Jak3 (leukocyte-JAK), are expressed in most tissues (reviewed in). This kinase family features seven conserved JAK homology (JH) domains, notably including a tandem set of carboxy terminal kinase domains, where only JH1 has bona fide catalytic activity (Ki). JH2 is referred to as the pseudo kinase (ψKi) domain. Reminiscent of other kinases, activation is driven by phosphorylation of critical tyrosines in the inactivation loop, which releases its blockade of the catalytic site. Although no function has been assigned to the SH2-related domain (“SH2”; JH5 and half of JH4), the amino terminal domains (JH1-3 and half of JH4) constitute a FERM (four point one, ezrin, radixin, moesin) domain, which directs stable association with membrane proximal receptor motifs. 

Members of the Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) are activated by ligands binding to a number of associated cytokine receptors. Upon cytokine receptor activation, Jak proteins become autophosphorylated and phosphorylate their associated receptors to provide multiple binding sites for signaling proteins. These associated signaling proteins, such as Stats, Shc, insulin receptor substrates, and focal adhesion kinase (FAK), typically contain SH2 or other phospho-tyrosine-binding domains.