Tec family protein-tyrosine kinases and pleckstrin homology domains in mast cells.

Tec family protein-tyrosine kinases (PTKs) have been recognized as a distinct subfamily for only a few years. Two of them, Btk and Emt, are tyrosine-phosphorylated and enzymatically activated upon cross-linking of the high-affinity IgE receptor (Fc epsilonRI), suggesting their involvement in mast cell activation. Since Lyn and other Src family PTKs phosphorylate Btk at Tyr-551 and activate the latter kinase, the receptor-associated Lyn seems to activate Btk in mast cells. The Btk kinase activity, on the other hand, is regulated negatively by phosphorylation by protein kinase C (PKC) that is associated with Btk via Btk's pleckstrin homology (PH) domain. PH domains also bind to phospholipids and the beta subunit of heterotrimeric GTP-binding proteins. Therefore, it has been hypothesized that PH domains play roles in membrane localization.