A Bipolar Clamp Mechanism for Activation of Jak-Family Protein Tyrosine Kinases
Figure 5
Membrane localization and dimerization of SH2-Bβ synergize to enhance the potency of its Jak2 activation-promoting function.
Steady-state calculations were performed using the Extended Cellular Model and the same parameter values as in Figure 4B. The total concentration of phosphoinositide, on a whole-cell basis, is either 0, 100 nM, or 1 µM as indicated, and its recruitment of SH2-Bβ PH domain is characterized by KD,SP = 100 nM. Two scenarios are considered: full-length SH2-Bβ (A and B) and SH2-Bβ with the dimerization domain absent (C and D). The calculated quantities are receptor-bound, phosphorylated Jak2 (Y2∼P; A and C) and total receptor-bound Jak2 (B and D).