The catalytic subunit of phosphoinositide 3-kinase: Requirements for oncogenicity

被引:73
|
作者
Aoki, M [1 ]
Schetter, C [1 ]
Himly, M [1 ]
Batista, O [1 ]
Chang, HW [1 ]
Vogt, PK [1 ]
机构
[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
关键词
D O I
10.1074/jbc.275.9.6267
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The retroviral oncogene p3k (v-p3k) of avian sarcoma virus 16 (ASV16) codes for the catalytic subunit of phosphoinositide (PI) 3-kinase, p110 alpha. The v-P3k protein is oncogenic in vivo and in vitro; its cellular counterpart, c-P3k, lacks oncogenicity, Fusion of viral Gag sequences to the amino terminus of c-P3k activates the transforming potential, Activation can also be achieved by the addition of a myristylation signal to the amino terminus or of a farnesylation signal to the carboxyl terminus of c-P3k, A mutated myristylation signal was equally effective; it also caused a strong increase in the kinase activity of P3k, Mutations that inactivate lipid kinase activity abolish oncogenicity, The transforming activity of P3k is correlated with the ability to induce activating phosphorylation in Akt. Point mutations and amino-terminal deletions recorded in v-P3k were shown to be irrelevant to the activation of oncogenic potential, Interactions of P3k with the regulatory subunit of PI 3-kinase, p85, or with Pas are not required for transformation, These results support the conclusion that the oncogenicity of P3k depends on constitutive lipid kinase activity. Akt is an important and probably essential downstream component of the oncogenic signal from P3k.
引用
收藏
页码:6267 / 6275
页数:9
相关论文
共 50 条
  • [41] Modulation of phagosome phosphoinositide dynamics by a Legionella phosphoinositide 3-kinase
    Li, Gen
    Liu, Hongtao
    Luo, Zhao-Qing
    Qiu, Jiazhang
    EMBO REPORTS, 2021, 22 (03)
  • [42] Cancer-derived mutations in the regulatory subunit p85α of phosphoinositide 3-kinase function through the catalytic subunit p110α
    Sun, Minghao
    Hillmann, Petra
    Hofmann, Bianca T.
    Hart, Jonathan R.
    Vogt, Peter K.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (35) : 15547 - 15552
  • [43] Direct interaction of retinal insulin receptor β-subunit with p85 subunit of phosphoinositide 3-kinase in vivo
    Rajala, RVS
    McClellan, ME
    Tsiokas, L
    Anderson, RE
    FASEB JOURNAL, 2003, 17 (04): : A169 - A169
  • [44] Involvement of regulatory and catalytic subunits of phosphoinositide 3-kinase in NF-κB activation
    Béraud, C
    Henzel, WJ
    Baeuerle, PA
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (02) : 429 - 434
  • [45] Phosphoinositide 3-kinase inhibition in cancer treatment
    Berrie, CP
    EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2001, 10 (06) : 1085 - 1098
  • [46] A role for phosphoinositide 3-kinase in bacterial invasion
    Ireton, K
    Payrastre, B
    Chap, H
    Ogawa, W
    Sakaue, H
    Kasuga, M
    Cossart, P
    SCIENCE, 1996, 274 (5288) : 780 - 782
  • [48] Phosphoinositide 3-kinase dependent carcinogenesis in the liver
    Tsolova, Dayana
    Ulrich, Angelika
    Saur, Dieter
    JOURNAL OF HEPATOLOGY, 2021, 75 : S509 - S509
  • [49] A role for phosphoinositide 3-kinase δ in neutrophil trafficking
    Puri, K
    Doggett, T
    Douangpanya, J
    Hou, Y
    Tino, W
    Wilson, T
    Graf, T
    Clayton, E
    Turner, M
    Hayflick, J
    Diacovo, T
    IMMUNOLOGY 2004: CYTOKINE NETWORK, REGULATORY CELLS, SIGNALING, AND APOPTOSIS, 2004, : 303 - 307
  • [50] Phosphoinositide 3-kinase signaling in the vertebrate retina
    Rajala, Raju V. S.
    JOURNAL OF LIPID RESEARCH, 2010, 51 (01) : 4 - 22