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Involvement of sphingomyelinase in insulin‐induced phosphatidylinositol 3‐kinase activation
Author(s) -
Huang Chuanshu,
Ma Wei-Ya,
Ding Min,
Li Jingxia,
Shi Xianglin,
Castranova Vincent,
Vallyathan Val,
Bode Ann M.,
Dong Zigang
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fsb2fj000520fje
Subject(s) - wortmannin , phosphatidylinositol , microbiology and biotechnology , ceramide , kinase , chemistry , cyclin dependent kinase 9 , insulin receptor , map kinase kinase kinase , mitogen activated protein kinase kinase , insulin , biology , protein kinase a , biochemistry , endocrinology , insulin resistance , apoptosis
Insulin plays a key role in regulating a wide range of cellular functions. Most functions of insulin are believed to occur through activation of phosphatidylinositol‐3 kinase (PI‐3 kinase) signaling pathways. The present study demonstrates that insulin, C2‐ceramide, or phosphocholine (PCho) induced a strong activation of PI‐3 kinase activity. This activation was dramatically inhibited by either pretreatment of cells with wortmannin, a widely used PI‐3 kinase inhibitor, or constitutive overexpression of a dominant negative p85 subunit of PI‐3 kinase (ΔΡ85). Insulin‐induced activation of PI‐3 kinase was observed only in the normal human lymphoblast cell line, JY, but not in the sphingomyelinase (SMase)‐deficient cell line, MS1418. The PI‐3 kinase activation in MS1418 cells could be restored by exposure of the cells to either SMase, C2‐ceramide, or PCho. These data provide direct evidence that SMase and its products act as mediators in insulin‐induced activation of PI‐3 kinase.