PMID- 20015408
OWN - NLM
STAT- MEDLINE
DCOM- 20100222
LR  - 20211020
IS  - 1471-213X (Electronic)
IS  - 1471-213X (Linking)
VI  - 9
DP  - 2009 Dec 17
TI  - Evidence that phosphatidylinositol 3-kinase is involved in sperm-induced tyrosine 
      kinase signaling in Xenopus egg fertilization.
PG  - 68
LID - 10.1186/1471-213X-9-68 [doi]
AB  - BACKGROUND: Studies have examined the function of PI 3-kinase in the early 
      developmental processes that operate in oocytes or early embryos of various 
      species. However, the roles of egg-associated PI 3-kinase and Akt, especially in 
      signal transduction at fertilization, are not well understood. RESULTS: Here we 
      show that in Xenopus eggs, a potent inhibitor of phosphatidylinositol 3-kinase 
      (PI 3-kinase), LY294002 inhibits sperm-induced activation of the tyrosine kinase 
      Src and a transient increase in the intracellular concentration of Ca2+ at 
      fertilization. LY294002 also inhibits sperm-induced dephosphorylation of 
      mitogen-activated protein kinase, breakdown of cyclin B2 and Mos, and first 
      embryonic cleavage, all of which are events of Ca2+-dependent egg activation. In 
      fertilized eggs, an 85-kDa subunit of PI 3-kinase (p85) undergoes a transient 
      translocation to the low-density, detergent-insoluble membranes (membrane 
      microdomains) where Src tyrosine kinase signaling is operating. However, the 
      tyrosine phosphorylation of p85 in fertilized eggs is not as evident as that in 
      H2O2-activated eggs, arguing against the possibility that PI 3-kinase is 
      activated by Src phosphorylation. Nevertheless, sperm-induced activation of PI 
      3-kinase has been demonstrated by the finding that Akt, a 
      serine/threonine-specific protein kinase, is phosphorylated at threonine-308. The 
      threonine-phosphorylated Akt also localizes to the membrane microdomains of 
      fertilized eggs. Application of bp(V), an inhibitor of PTEN that dephosphorylates 
      PIP3, the enzymatic product of PI 3-kinase, promotes parthenogenetic activation 
      of Xenopus eggs. In vitro kinase assays demonstrate that PIP3 activates Src in a 
      dose-dependent manner. CONCLUSIONS: These results suggest that PI 3-kinase is 
      involved in sperm-induced egg activation via production of PIP3 that would act as 
      a positive regulator of the Src signaling pathway in Xenopus fertilization.
FAU - Mammadova, Gunay
AU  - Mammadova G
AD  - The Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 
      657-8501, Japan. l1981@yahoo.com
FAU - Iwasaki, Tetsushi
AU  - Iwasaki T
FAU - Tokmakov, Alexander A
AU  - Tokmakov AA
FAU - Fukami, Yasuo
AU  - Fukami Y
FAU - Sato, Ken-ichi
AU  - Sato K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091217
PL  - England
TA  - BMC Dev Biol
JT  - BMC developmental biology
JID - 100966973
RN  - 0 (Chromones)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chromones/pharmacology
MH  - *Fertilization
MH  - Humans
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - *Signal Transduction
MH  - Xenopus/embryology/*metabolism
MH  - src-Family Kinases/*metabolism
PMC - PMC2805626
EDAT- 2009/12/18 06:00
MHDA- 2010/02/23 06:00
PMCR- 2009/12/17
CRDT- 2009/12/18 06:00
PHST- 2009/03/31 00:00 [received]
PHST- 2009/12/17 00:00 [accepted]
PHST- 2009/12/18 06:00 [entrez]
PHST- 2009/12/18 06:00 [pubmed]
PHST- 2010/02/23 06:00 [medline]
PHST- 2009/12/17 00:00 [pmc-release]
AID - 1471-213X-9-68 [pii]
AID - 10.1186/1471-213X-9-68 [doi]
PST - epublish
SO  - BMC Dev Biol. 2009 Dec 17;9:68. doi: 10.1186/1471-213X-9-68.