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Two distinct phosphoinositide 3‐kinases mediate polypeptide growth factor‐stimulated PKB activation
Author(s) -
Arcaro Alexandre,
Khanzada Umme K.,
Vanhaesebroeck Bart,
Tetley Teresa D.,
Waterfield Michael D.,
Seckl Michael J.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf512
Subject(s) - library science , biology , computer science
Eight human isoforms of phosphoinositide 3‐kinases (PI3Ks) exist, but their individual functions remain poorly understood. Here, we show that different human small cell lung carcinoma (SCLC) cell lines overexpress distinct subsets of class I A and II PI3Ks, which results in striking differences in the signalling cascades activated by stem cell factor (SCF). Over expression of class I A p85/p110α in SCLC cells increased SCF‐stimulated protein kinase B (PKB) activation and cell growth, but did not affect extracellular signal‐regulated kinase (Erk) or glycogen synthase kinase‐3 (GSK‐3). This effect was selective, since it was not observed in SCLC cell lines overexpressing p85/p110β or p85/p110δ. The SCF receptor associated with both class I A p85 and class II PI3KC2β, and both enzymes contributed to SCF‐stimulated PKB activity. A dominant‐negative PI3KC2β blocked both PKB activation and SCLC cell growth in response to SCF. Together our data provide novel insights into the specificity and functional significance of PI3K signalling in human cancer.