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Biochem J
2007 Jan 15;4012:521-31. doi: 10.1042/BJ20061287.
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Phosphorylation of the proline-rich domain of Xp95 modulates Xp95 interaction with partner proteins.
Dejournett RE
,
Kobayashi R
,
Pan S
,
Wu C
,
Etkin LD
,
Clark RB
,
Bögler O
,
Kuang J
.
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The mammalian adaptor protein Alix [ALG-2 (apoptosis-linked-gene-2 product)-interacting protein X] belongs to a conserved family of proteins that have in common an N-terminal Bro1 domain and a C-terminal PRD (proline-rich domain), both of which mediate partner protein interactions. Following our previous finding that Xp95, the Xenopus orthologue of Alix, undergoes a phosphorylation-dependent gel mobility shift during progesteroneinduced oocyte meiotic maturation, we explored potential regulation of Xp95/Alix by protein phosphorylation in hormone-induced cell cycle re-entry or M-phase induction. By MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS analyses and gel mobility-shift assays, Xp95 is phosphorylated at multiple sites within the N-terminal half of the PRD during Xenopus oocyte maturation, and a similar region in Alix is phosphorylated in mitotically arrested but not serum-stimulated mammalian cells. By tandem MS, Thr745 within this region, which localizes in a conserved binding site to the adaptor protein SETA [SH3 (Src homology 3) domain-containing, expressed in tumorigenic astrocytes] CIN85 (a-cyano-4-hydroxycinnamate)/SH3KBP1 (SH3-domain kinase-binding protein 1), is one of the phosphorylation sites in Xp95. Results from GST (glutathione S-transferase)-pull down and peptide binding/competition assays further demonstrate that the Thr745 phosphorylation inhibits Xp95 interaction with the second SH3 domain of SETA. However, immunoprecipitates of Xp95 from extracts of M-phase-arrested mature oocytes contained additional partner proteins as compared with immunoprecipitates from extracts of G2-arrested immature oocytes. The deubiquitinase AMSH (associated molecule with the SH3 domain of signal transducing adaptor molecule) specifically interacts with phosphorylated Xp95 in M-phase cell lysates. These findings establish that Xp95/Alix is phosphorylated within the PRD during M-phase induction, and indicate that the phosphorylation may both positively and negatively modulate their interaction with partner proteins.
Agromayor,
Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo.
2006, Pubmed
Agromayor,
Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo.
2006,
Pubmed
Barr,
Inheritance of the endoplasmic reticulum and Golgi apparatus.
2002,
Pubmed
Bellé,
Protein phosphorylation during meiotic maturation of Xenopus oocytes: cdc2 protein kinase targets.
1990,
Pubmed
,
Xenbase
Birge,
SH2 and SH3-containing adaptor proteins: redundant or independent mediators of intracellular signal transduction.
1996,
Pubmed
Borinstein,
SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins.
2000,
Pubmed
Chatellard-Causse,
Alix (ALG-2-interacting protein X), a protein involved in apoptosis, binds to endophilins and induces cytoplasmic vacuolization.
2002,
Pubmed
Che,
Identification and cloning of xp95, a putative signal transduction protein in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Che,
MPM-2 epitope sequence is not sufficient for recognition and phosphorylation by ME kinase-H.
1997,
Pubmed
,
Xenbase
Chen,
The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes.
2000,
Pubmed
,
Xenbase
Dikic,
CIN85/CMS family of adaptor molecules.
2002,
Pubmed
Ferrell,
Xenopus oocyte maturation: new lessons from a good egg.
1999,
Pubmed
,
Xenbase
Gaston,
Coexistence of phosphotyrosine-dependent and -independent interactions between Cbl and Bcr-Abl.
2004,
Pubmed
Harvey,
Cdk1-dependent regulation of the mitotic inhibitor Wee1.
2005,
Pubmed
Katoh,
The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting.
2003,
Pubmed
Katoh,
CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms.
2004,
Pubmed
Kim,
Structural basis for endosomal targeting by the Bro1 domain.
2005,
Pubmed
Kodama,
Coordinating cytoskeletal tracks to polarize cellular movements.
2004,
Pubmed
Kowanetz,
Identification of a novel proline-arginine motif involved in CIN85-dependent clustering of Cbl and down-regulation of epidermal growth factor receptors.
2003,
Pubmed
Liang,
Herpes simplex virus 1 infected cell protein 0 forms a complex with CIN85 and Cbl and mediates the degradation of EGF receptor from cell surfaces.
2005,
Pubmed
Liu,
APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes.
2002,
Pubmed
Maller,
MPF and cell cycle control.
1990,
Pubmed
,
Xenbase
Matsuo,
Role of LBPA and Alix in multivesicular liposome formation and endosome organization.
2004,
Pubmed
Nakamura,
Clathrin anchors deubiquitinating enzymes, AMSH and AMSH-like protein, on early endosomes.
2006,
Pubmed
Nebreda,
Regulation of the meiotic cell cycle in oocytes.
2000,
Pubmed
,
Xenbase
Pan,
Involvement of the conserved adaptor protein Alix in actin cytoskeleton assembly.
2006,
Pubmed
Sakaguchi,
AIP1/Alix is a binding partner of Sendai virus C protein and facilitates virus budding.
2005,
Pubmed
Scaife,
The multi-adaptor proto-oncoprotein Cbl is a key regulator of Rac and actin assembly.
2003,
Pubmed
Schmidt,
Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners and antagonizes its activities.
2005,
Pubmed
Schmidt,
SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion.
2003,
Pubmed
,
Xenbase
Schmidt,
Alix/AIP1 antagonizes epidermal growth factor receptor downregulation by the Cbl-SETA/CIN85 complex.
2004,
Pubmed
Schmitt,
Signalling pathways in oocyte meiotic maturation.
2002,
Pubmed
,
Xenbase
Schweitzer,
Endocytosis resumes during late mitosis and is required for cytokinesis.
2005,
Pubmed
Segura-Morales,
Tsg101 and Alix interact with murine leukemia virus Gag and cooperate with Nedd4 ubiquitin ligases during budding.
2005,
Pubmed
Steen,
Phosphorylation analysis by mass spectrometry: myths, facts, and the consequences for qualitative and quantitative measurements.
2006,
Pubmed
Strack,
AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding.
2003,
Pubmed
Tsang,
A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.
2006,
Pubmed
von Schwedler,
The protein network of HIV budding.
2003,
Pubmed
Wu,
Overexpression of Hp95 induces G1 phase arrest in confluent HeLa cells.
2001,
Pubmed
,
Xenbase
Zell,
Regulation of beta 1-integrin-mediated cell adhesion by the Cbl adaptor protein.
1998,
Pubmed
Zeller,
The impact of chromatography and mass spectrometry on the analysis of protein phosphorylation sites.
2004,
Pubmed
