INPP4A/INPP4B and P-Rex proteins: Related but different?

Natalie Rynkiewicz, Tina Liu, Demosthenes Balamatsias, Christina Anne Mitchell

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Phosphoinositide 3-kinase (PI3K) signaling is activated downstream of tyrosine kinase receptors (RTKs a?? class IA) and G-protein coupled receptors (GPCRs - class IB) to generate 3a??OH phosphorylated phosphoinositides ( [Fruman et al., 1998] and Hawkins et al., 2006 P.T. Hawkins, K.E. Anderson, K. Davidson and L.R. Stephens, Signalling through Class I PI3Ks in mammalian cells. Biochem Soc Trans, 34 (2006), pp. 647a??662. View Record in Scopus Cited By in Scopus (191)[Hawkins et al., 2006] ). Following its activation, PI3K phosphorylates PtdIns(4,5)P2 to form PtdIns(3,4,5)P3, which is rapidly dephosphorylated either by PTEN (phosphatase and tensin homologue deleted on chromosome 10) to PtdIns(4,5)P2, or by members of the inositol polyphosphate 5-phosphatase (5-phosphatase) family, generating PtdIns(3,4)P2 ( [Ooms et al., 2009] and [Vanhaesebroeck et al., 2010] ). PtdIns(3,4,5)P3 and PtdIns(3,4)P2 are membrane-bound signaling molecules that recruit many downstream effectors to the plasma membrane and facilitate their activation, the most prominent being the serinea??threonine kinase Akt, which promotes cell growth and survival pathways ( [Brazil et al., 2004] and [Fayard et al., 2010] ). Akt binds PtdIns(3,4,5)P3 and PtdIns(3,4)P2 with equal affinity in vitro ( [Franke et al., 1997] , [Frech et al., 1997] and [James et al., 1996] ), and in vivo both phosphoinositides are necessary for full Akt activation, which occurs via PDK1 phosphorylation of Akt at Thr308 and via the mammalian target of rapamycin complex 2 (mTORC2), which phosphorylates Akt on Ser473 ( [Mora et al., 2004] and [Sarbassov et al., 2005] ). Activated Akt (pAkt) in turn phosphorylates many downstream targets stimulating cell proliferation and survival ( [Brazil et al., 2004] and [Fayard et al., 2010] ). Oncogenic mutations in the PI3K gene, PIK3CA, have been identified in many human tumors, resulting in activation of Akt and other PtdIns(3,4,5)P3/PtdIns(3,4)P2 effectors (Ligresti et al., 2009)
Original languageEnglish
Pages (from-to)265 - 279
Number of pages15
JournalAdvances in Enzyme Regulation
Volume52
Issue number1
DOIs
Publication statusPublished - 2012

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