The NH2-terminal region of focal adhesion kinase reconstitutes high affinity IgE receptor-induced secretion in mast cells

Focal adhesion kinase (FAK) is tyrosine-phosphorylated by adherence of cell s and also by Fc epsilon RI aggregation in RBL-2H3 mast cells. Using phosph orylation site-specific antibodies, we observed that Fc epsilon RI activati on in these cells led to an increase in FAK phosphorylation at the same tyr osine residues that are phosphorylated by integrin-induced activation. Prev ious studies in the 3B6 line, a FAK-deficient variant of the RBL-2H3 cells, suggest that FAK plays a role in Fc epsilon RI-induced secretion. Stable c ell lines expressing either full-length or truncated forms of FAK were isol ated after transfection of the FAK-deficient 3B6 variant cells. The NH2 dom ain of FAK, which lacks the enzymatic and the COOH-terminal regions, was su fficient to reconstitute secretion. The different truncated forms of FAK we re still tyrosine-phosphorylated after Fc epsilon RI aggregation. Therefore , the kinase domain and the COOH-terminal region are not essential for Fc e psilon RI-induced tyrosine phosphorylation of FAK or for secretion. Taken t ogether, our data demonstrate that the reconstitution of secretion is disso ciated from FAK activation and that the NH2-terminal region of FAK is the o nly critical element that may play a role in Fc epsilon RI-induced secretio n by acting as an adaptor or linker molecule.