title: Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases.
abstract: The interaction of talin with phosphatidylinositol(4) phosphate 5 kinase type I gamma (PIPKI gamma) regulates PI(4,5)P2 synthesis at synapses and at focal adhesions. Here, we show that phosphorylation of serine 650 (S650) within the talin-binding sequence of human PIPKI gamma blocks this interaction. At synapses, S650 is phosphorylated by p35/Cdk5 and mitogen-activated protein kinase at rest, and dephosphorylated by calcineurin upon stimulation. S650 is also a substrate for cyclin B1/Cdk1 and its phosphorylation in mitosis correlates with focal adhesion disassembly. Phosphorylation by Src of the tyrosine adjacent to S650 (Y649 in human PIPKI gamma) was shown to enhance PIPKI gamma targeting to focal adhesions (Ling, K., R.L. Doughman, V.V. Iyer, A.J. Firestone, S.F. Bairstow, D.F. Mosher, M.D. Schaller, and R.A. Anderson. 2003. J. Cell Biol. 163:1339-1349). We find that Y649 phosphorylation does not stimulate directly PIPKI gamma binding to talin, but may do so indirectly by inhibiting S650 phosphorylation. Conversely, S650 phosphorylation inhibits Y649 phosphorylation by Src. The opposite effects of the phosphorylation of Y649 and S650 likely play a critical role in regulating synaptic function as well as the balance between cell adhesion and cell motility.
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Lee
authors.forename: Sergey
authors.initials: S
authors.lastname: Voronov
authors.forename: Kresimir
authors.initials: K
authors.lastname: Letinic
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Gilbert
authors.initials: G
authors.lastname: Di Paolo
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D019703:Calcineurin / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006801:Humans; D008938:Mitosis / Q000502:physiology; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D038461:Proline-Directed Protein Kinases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D016608:Talin / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D016608:Talin; D012694:Serine; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D019061:src-Family Kinases; D038461:Proline-Directed Protein Kinases; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases; D019703:Calcineurin
references.citation: Cell. 1999 Oct 15;99(2):179-88
references.pmid: 10535736
references.citation: J Biol Chem. 2005 Mar 4;280(9):8381-6
references.pmid: 15623515
references.citation: J Biol Chem. 2001 Feb 16;276(7):4781-7
references.pmid: 11087761
references.citation: J Biol Chem. 2001 Mar 16;276(11):8104-10
references.pmid: 11113134
references.citation: J Biol Chem. 2001 Jun 15;276(24):21217-27
references.pmid: 11279249
references.citation: Nat Rev Mol Cell Biol. 2001 Oct;2(10):749-59
references.pmid: 11584302
references.citation: J Neurosci. 2001 Oct 15;21(20):7944-53
references.pmid: 11588168
references.citation: Neuron. 2001 Oct 11;32(1):79-88
references.pmid: 11604140
references.citation: Trends Neurosci. 2001 Nov;24(11):659-65
references.pmid: 11672811
references.citation: Biochim Biophys Acta. 2001 Oct 31;1533(3):190-206
references.pmid: 11731330
references.citation: J Neurochem. 2002 Mar;80(5):835-42
references.pmid: 11948247
references.citation: Cell. 2002 Sep 20;110(6):673-87
references.pmid: 12297042
references.citation: Nature. 2002 Nov 7;420(6911):85-9
references.pmid: 12422219
references.citation: Nature. 2002 Nov 7;420(6911):89-93
references.pmid: 12422220
references.citation: Mol Cancer Res. 2002 Nov;1(1):12-24
references.pmid: 12496365
references.citation: J Biol Chem. 2003 Jan 10;278(2):1186-94
references.pmid: 12417592
references.citation: Mol Cell. 2003 Jan;11(1):49-58
references.pmid: 12535520
references.citation: J Cell Biol. 2003 Jan 20;160(2):255-65
references.pmid: 12538643
references.citation: Annu Rev Physiol. 2003;65:761-89
references.pmid: 12471164
references.citation: Curr Biol. 2003 Feb 4;13(3):R94-5
references.pmid: 12573235
references.citation: EMBO J. 2003 Jul 1;22(13):3279-90
references.pmid: 12839990
references.citation: J Cell Biol. 2003 Jul 7;162(1):113-24
references.pmid: 12847086
references.citation: Nat Cell Biol. 2003 Aug;5(8):701-10
references.pmid: 12855954
references.citation: Nat Cell Biol. 2003 Aug;5(8):694-7
references.pmid: 12894175
references.citation: J Biol Chem. 2003 Aug 15;278(33):31202-9
references.pmid: 12782621
references.citation: J Cell Biol. 2003 Aug 18;162(4):647-59
references.pmid: 12925709
references.citation: Cell. 2003 Aug 22;114(4):469-82
references.pmid: 12941275
references.citation: J Membr Biol. 2003 Jul 15;194(2):77-89
references.pmid: 14502432
references.citation: Trends Neurosci. 2003 Nov;26(11):625-30
references.pmid: 14585603
references.citation: J Cell Biol. 2003 Nov 24;163(4):813-24
references.pmid: 14623869
references.citation: J Am Chem Soc. 2003 Dec 3;125(48):14859-66
references.pmid: 14640663
references.citation: J Cell Biol. 2003 Dec 22;163(6):1339-49
references.pmid: 14691141
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):546-51
references.pmid: 14704270
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1112-3
references.pmid: 14745021
references.citation: Biochem J. 2004 Apr 15;379(Pt 2):489-96
references.pmid: 14741049
references.citation: Trends Cell Biol. 2004 May;14(5):241-9
references.pmid: 15130580
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8262-9
references.pmid: 15146067
references.citation: J Biol Chem. 2004 Jul 9;279(28):28889-95
references.pmid: 15143061
references.citation: Nature. 2004 Sep 23;431(7007):415-22
references.pmid: 15386003
references.citation: J Cell Biol. 2004 Oct 11;167(1):43-50
references.pmid: 15479735
references.citation: J Cell Biol. 1991 Sep;114(6):1159-66
references.pmid: 1910051
references.citation: Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6486-90
references.pmid: 8022809
references.citation: Curr Biol. 1995 Mar 1;5(3):283-95
references.pmid: 7780739
references.citation: Science. 1996 Mar 15;271(5255):1533-9
references.pmid: 8599109
references.citation: J Biol Chem. 1996 May 31;271(22):13197-201
references.pmid: 8662672
references.citation: Mol Cell Biol. 1996 Nov;16(11):6486-93
references.pmid: 8887677
references.citation: J Biol Chem. 1997 Dec 5;272(49):30984-92
references.pmid: 9388246
references.citation: J Biol Chem. 1998 Apr 10;273(15):8741-8
references.pmid: 9535851
references.citation: Annu Rev Cell Dev Biol. 1998;14:231-64
references.pmid: 9891784
references.citation: J Biol Chem. 1999 Feb 5;274(6):3257-60
references.pmid: 9920862
references.citation: J Biol Chem. 1999 Apr 23;274(17):11977-86
references.pmid: 10207019
references.citation: J Biol Chem. 1999 Oct 1;274(40):28071-4
references.pmid: 10497155
references.citation: Nature. 1999 Dec 9;402(6762):615-22
references.pmid: 10604467