Impaired Kit- but Not FcεRI-initiated Mast Cell Activation in the Absence of Phosphoinositide 3-Kinase p85α Gene Products*
By J. Lu-Kuo, D. Fruman, D. M. Joyal, Lewis C. Cantley, H. Katz. Journal of Biological Chemistry, 2000
84 citations recorded by the source corpus.
The class IAphosphoinositide 3-kinases (PI3Ks) consist of a 110-kDa catalytic domain and a regulatory subunit encoded by the p85α, p85β, or p55γ genes. We have determined the effects of disrupting the p85α gene on the responses of mast cells stimulated by the cross-linking of Kit and FcεRI, receptors that reflect innate and adaptive responses, respectively. The absence of p85α gene products partially inhibited Kit ligand/stem cell factor-induced secretory granule exocytosis, proliferation, and phosphorylation of the serine/threonine kinase Akt. In contrast, p85α gene products were not required for FcεRI-initiated exocytosis and phosphorylation of Akt. LY294002, which inhibits all classes of PI3Ks, strongly suppressed Kit- and FcεRI-induced responses in p85α −/− mast cells, revealing the contribution of another PI3K family member(s). In contrast to B lymphocytes, mast cell proliferation was not dependent on Bruton's tyrosine kinase, a downstream effector of PI3K, revealing a distinct pathway of PI3K-dependent proliferation in mast cells. Our findings represent the first example of receptor-specific usage of different PI3K family members in a single cell type. In addition, because Kit- but not FcεRI-initiated signaling is associated with mast cell proliferation, the results provide evidence that distinct biologic functions signaled by these two receptors may reflect differential usage of PI3Ks.
Subfields: Immunology, Molecular Biology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/305b7cbff881b531508563375b6dcb98758504ac
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In Immunology
Citations in the corpus
- Scaffolding Adapter Grb2-Associated Binder 2 Requires Syk to Transmit Signals from FcεRI1 (2006, methodology): “Supernatants were assayed for -hexosaminidase activity as described (30).”