A Bipolar Clamp Mechanism for Activation of Jak-Family Protein Tyrosine Kinases
Figure 3
SH2-Bβ significantly enhances GH receptor-mediated Jak2 autophosphorylation in vivo.
Steady-state calculations were performed using the Simplified Cellular Model, with equal Jak2 and SH2-Bβ concentrations and KD values (JTot = STot = KD,JS = KD,SS = 100 nM). In the SH2-B null case, STot = 0, and in the DD-mutated SH2-B case, KD,SS = infinity; these two cases are functionally equivalent (and therefore the curves lie on top of one another). (A) SH2-Bβ does not affect GH dose-dependent receptor-dimerization (all of the filled symbols in panel A lie approximately on top of one another) but mediates ∼3-fold improvement in pair-wise recruitment of Jak2 to receptors (the number of Jak2 molecules engaged in receptor-Jak2 complexes containing two Jak2). (B) Accordingly, SH2-Bβ enhances Jak2 autophosphorylation (site Y2) by roughly 3-fold.