Figure 2. SH2-domain dependent positive feed-back loop on catalytic activity of c-Abl.

Figure 2

SH2-domain dependent positive feed-back loop on catalytic activity of c-Abl. From top to bottom, the cartoon shows a possible order of event in the activation of c-Abl by SH2 domain engagement. An initial phosphorylation event may arise through basal activity of the enzyme and accessibility of a particular substrate to the Abl kinase domain. Any of the positive events listed in Fig. 3 may apply as well, as, for example, engagement of the SH3 domain by a binder competing with the intramolecular interactions. Once, phosphorylated, a substrate may engage the SH2 domain of the Abl kinase, leading to a higher and more stable level of activity. This in turn, may result in phosphorylation of additional sites within the same substrate molecule or of adjacent proteins. These sites may represent even better or just additional binding partners for the same or other Abl proteins. SH2-domain dependent “processive” phosphorylation has been described previously in vitro as well as in vivo.39-41 Engagement of a tyrosine phosphatase may efficiently oppose the process.

From: Mechanisms of Activation of Abl Family Kinases

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