Protein kinase Cν/protein kinase D3 nuclear localization, catalytic activation, and intracellular redistribution in response to G protein-coupled receptor agonists

被引:81
作者
Rey, O
Yuan, JZ
Young, SH
Rozengurt, E
机构
[1] Univ Calif Los Angeles, Sch Med,CURE Digest Dis Res Ctr, Dept Med,Div Digest Dis, Unit Signal Transduct & Gastrointestinal Canc, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Biol, Los Angeles, CA 90095 USA
关键词
D O I
10.1074/jbc.M300226200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The protein kinase D (PKD) family consists of three serine/threonine kinases: PKCmu/PKD, PKD2, and PKCnu/PKD3. Whereas PKD has been the focus of most studies, virtually nothing is known about the effect of G protein-coupled receptor agonists ( GPCR) on the regulatory properties and intracellular distribution of PKD3. Consequently, we examined the mechanism that mediates its activation and intracellular distribution. GPCR agonists induced a rapid activation of PKD3 by a protein kinase C (PKC)-dependent pathway that leads to the phosphorylation of the activation loop of PKD3. Comparison of the steady-state distribution of endogenous or tagged PKD3 versus PKD and PKD2 in unstimulated cells indicated that whereas PKD and PKD2 are predominantly cytoplasmic, PKD3 is present both in the nucleus and cytoplasm. This distribution of PKD3 results from its continuous shuttling between both compartments by a mechanism that requires a nuclear import receptor and a competent CRM1-nuclear export pathway. Cell stimulation with the GPCR agonist neurotensin induced a rapid and reversible plasma membrane translocation of PKD3 that is PKC-dependent. Interestingly, the nuclear accumulation of PKD3 can be dramatically enhanced in response to its activation. Thus, this study demonstrates that the intracellular distribution of PKD isoenzymes are distinct, and suggests that their signaling properties are regulated by differential localization.
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页码:23773 / 23785
页数:13
相关论文
共 92 条
[1]   Rapid activation of the novel serine/threonine protein kinase, protein kinase D by phorbol esters, angiotensin II and PDGF-BB in vascular smooth muscle cells [J].
Abedi, H ;
Rozengurt, E ;
Zachary, I .
FEBS LETTERS, 1998, 427 (02) :209-212
[2]   Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor [J].
Bagowski, CP ;
Stein-Gerlach, M ;
Choidas, A ;
Ullrich, A .
EMBO JOURNAL, 1999, 18 (20) :5567-5576
[3]   Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2 [J].
Ben-Levy, R ;
Hooper, S ;
Wilson, R ;
Paterson, HF ;
Marshall, CJ .
CURRENT BIOLOGY, 1998, 8 (19) :1049-1057
[4]   An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation [J].
Bowden, ET ;
Barth, M ;
Thomas, D ;
Glazer, RI ;
Mueller, SC .
ONCOGENE, 1999, 18 (31) :4440-4449
[5]   Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX [J].
Brownawell, AM ;
Kops, GJPL ;
Macara, IG ;
Burgering, BMT .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (10) :3534-3546
[6]   Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells [J].
Clarke, JH ;
Letcher, AJ ;
D'Santos, CS ;
Halstead, JR ;
Irvine, RF ;
Divecha, N .
BIOCHEMICAL JOURNAL, 2001, 357 (03) :905-910
[7]   Regulation of nuclear localization during signaling [J].
Cyert, MS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (24) :20805-20808
[8]   Nuclei contain two differentially regulated pools of diacylglycerol [J].
D'Santos, CS ;
Clarke, JH ;
Irvine, RF ;
Divecha, N .
CURRENT BIOLOGY, 1999, 9 (08) :437-440
[9]   PROTEIN-KINASE-C - A QUESTION OF SPECIFICITY [J].
DEKKER, LV ;
PARKER, PJ .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (02) :73-77
[10]  
DEKKER LV, 1993, J BIOL CHEM, V268, P19498