Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases.
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.
Lee
Sang Yoon
SY
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Voronov
Sergey
S
Letinic
Kresimir
K
Nairn
Angus C
AC
Di Paolo
Gilbert
G
De Camilli
Pietro
P
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
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
Cell. 1999 Oct 15;99(2):179-88
10535736
J Biol Chem. 2005 Mar 4;280(9):8381-6
15623515
J Biol Chem. 2001 Feb 16;276(7):4781-7
11087761
J Biol Chem. 2001 Mar 16;276(11):8104-10
11113134
J Biol Chem. 2001 Jun 15;276(24):21217-27
11279249
Nat Rev Mol Cell Biol. 2001 Oct;2(10):749-59
11584302
J Neurosci. 2001 Oct 15;21(20):7944-53
11588168
Neuron. 2001 Oct 11;32(1):79-88
11604140
Trends Neurosci. 2001 Nov;24(11):659-65
11672811
Biochim Biophys Acta. 2001 Oct 31;1533(3):190-206
11731330
J Neurochem. 2002 Mar;80(5):835-42
11948247
Cell. 2002 Sep 20;110(6):673-87
12297042
Nature. 2002 Nov 7;420(6911):85-9
12422219
Nature. 2002 Nov 7;420(6911):89-93
12422220
Mol Cancer Res. 2002 Nov;1(1):12-24
12496365
J Biol Chem. 2003 Jan 10;278(2):1186-94
12417592
Mol Cell. 2003 Jan;11(1):49-58
12535520
J Cell Biol. 2003 Jan 20;160(2):255-65
12538643
Annu Rev Physiol. 2003;65:761-89
12471164
Curr Biol. 2003 Feb 4;13(3):R94-5
12573235
EMBO J. 2003 Jul 1;22(13):3279-90
12839990
J Cell Biol. 2003 Jul 7;162(1):113-24
12847086
Nat Cell Biol. 2003 Aug;5(8):701-10
12855954
Nat Cell Biol. 2003 Aug;5(8):694-7
12894175
J Biol Chem. 2003 Aug 15;278(33):31202-9
12782621
J Cell Biol. 2003 Aug 18;162(4):647-59
12925709
Cell. 2003 Aug 22;114(4):469-82
12941275
J Membr Biol. 2003 Jul 15;194(2):77-89
14502432
Trends Neurosci. 2003 Nov;26(11):625-30
14585603
J Cell Biol. 2003 Nov 24;163(4):813-24
14623869
J Am Chem Soc. 2003 Dec 3;125(48):14859-66
14640663
J Cell Biol. 2003 Dec 22;163(6):1339-49
14691141
Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):546-51
14704270
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1112-3
14745021
Biochem J. 2004 Apr 15;379(Pt 2):489-96
14741049
Trends Cell Biol. 2004 May;14(5):241-9
15130580
Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8262-9
15146067
J Biol Chem. 2004 Jul 9;279(28):28889-95
15143061
Nature. 2004 Sep 23;431(7007):415-22
15386003
J Cell Biol. 2004 Oct 11;167(1):43-50
15479735
J Cell Biol. 1991 Sep;114(6):1159-66
1910051
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6486-90
8022809
Curr Biol. 1995 Mar 1;5(3):283-95
7780739
Science. 1996 Mar 15;271(5255):1533-9
8599109
J Biol Chem. 1996 May 31;271(22):13197-201
8662672
Mol Cell Biol. 1996 Nov;16(11):6486-93
8887677
J Biol Chem. 1997 Dec 5;272(49):30984-92
9388246
J Biol Chem. 1998 Apr 10;273(15):8741-8
9535851
Annu Rev Cell Dev Biol. 1998;14:231-64
9891784
J Biol Chem. 1999 Feb 5;274(6):3257-60
9920862
J Biol Chem. 1999 Apr 23;274(17):11977-86
10207019
J Biol Chem. 1999 Oct 1;274(40):28071-4
10497155
Nature. 1999 Dec 9;402(6762):615-22
10604467