Studies on the biological function of Raf kinase inhibitor protein(rkip)

Size: px

Start display at page:

Download "Studies on the biological function of Raf kinase inhibitor protein(rkip)"

Cassandra Dean
5 years ago
Views:

1 Chinese Bulletin of Life Sciences Vol. 19, No. 1 Feb., (2007) Raf (RKIP) ( ) Raf Raf kinase inhibitor protein RKIP phosphatidylethanolamine-binding protein, PEBP RKIP Raf-1 MAPK G NF-κB RKIP RKIP Raf ; ; ; ; Q279 A Studies on the biological function of Raf kinase inhibitor protein(rkip) HU Xinzhou, WANG Xu, ZHANG Wei* (Ministry of Education Key Laboratory for Cell Proliferation and Regulation Biology, College of Life Sciences, Beijing Normal University, Beijing , China) Abstract: Raf kinase inhibitor protein (RKIP) is a member of the phosphatidylethanolamine -binding protein (PEBP) family, which is a widely expressed protein in a variety of different species. It plays a pivotal modulatory role in several intracellular signaling cascades. RKIP binds to Raf-1, and blocks MAPK signaling pathway. Also it has been demonstrated to regulate G-protein-coupled receptor signaling pathway and NF-κB signaling. RKIP plays a critical role in several physiological processes including membrane biosynthesis, spermatogenesis, neural development and apoptosis. It also contributes to pathophysiological processes including Alzheimer s disease and diabetic nephropathy. Additionally, recent researches show RKIP is a novel metastasis suppressor, which suppresses metastasis in prostate cancer, breast cancer and melanoma cancer. And RKIP becomes a novel prognostic marker in prostate cancer. key words: RKIP; signal transduction; prostate cancer; metastasis; apoptosis Bernier [1-2] PEBP [3-6] 1999 Yeung [7] PEBP Raf- 1 Raf-1/MEK/ERK RKIP RKIP G [8] ( ) (1981 ) , zhangwei@bnu.edu.cn (1969 ) * Tel:

2 32 NF-κΒ [9] RKIP [10] RKIP [11] 1 PEBP PEBP [3-6] PEBPs CEN(centroradialis) TF-1(terminal flower-1) SP(self-pruning) [3] Tfs1p [4] TES-26 [5] OBP(odorant binding protein) [6] 2002 Hickox [12] PEBPs pebp-1 pebp-2 pebp-3 RKIP pebp-1 Wang [13] PEBP hpebp4 [3,14] PEBPs( ) ( 1) β- β- C α- (phosphate-binding pocket) PEBP C α- PEBP GTP [14] 1 RKIP [14] 2 RKIP RKIP 12q24.23 mrna 1 507bp 4 Vallee [15] RKIP RKIP RKIP RKIP [11] 3 RKIP 3.1 RKIP Raf-1/MEK/ERK Yeung [7] RKIP Raf-1 MEK-1 ERK-2 RKIP Raf-1 MEK-1 Raf-1 MEK-1 RKIP Ras [7] RKIP Raf-1 MEK/ERK Yeung [16] RKIP Raf-1 MEK-1 Raf-1 MEK-1 RKIP Raf-1 MEK-1 Trakul [3] RKIP Raf-1 MEK Raf-1 MAPK Raf-1 RKIP Raf-1 PAK (p21-activated kinase) PAK Raf-1 [17] RKIP B-Raf RKIP B-Raf RKIP Raf-1 B-Raf MAPK [17] RKIP RKIP B-Raf RKIP B-Raf Raf-1 RKIP B-Raf RKIP

3 Raf (RKIP) 33 [18] Corbit [19] RKIP PKC Raf-1 PKC RKIP(Ser-153) RKIP Raf RKIP G RKIP G [20] GRK-2(G-protein-coupled receptor kinase-2) G (G-protein-coupled recepters, GPCR) GRK-2 GPCR G G Lorenz [8] RKIP GRK-2 GRK-2 GPCR PKC RKIP(Ser-153) [8,19] RKIP Raf-1 GRK-2 GRK-2 G Raf-1 Raf-1 / RKIP Raf-1 GRK-2 RKIP Raf-1 GRK-2 [8] 3.3 RKIP NF-κB Raf-1/MEK/ERK G RKIP NF-κB [9] MAPK RKIP NF-κB RKIP NF-κB RKIP NF-κB NIK (NF-κB inducing kinase) TAK1(TGF-β activated kinase 1) IKKα(IκB kinase α) IKKβ(IκB kinase β) NF-κB RKIP ERK ( Raf-1 MEK-1 ) [9] RKIP Raf-1/MEK/ERK G NF-κB ( 2) 2 RKIP A RKIP Raf NF-κB GRK-2 GPCR MAPK (1) RKIP Raf MAPK [7,16] (2) RKIP Raf Raf PAK PAK Raf MEK [17] B PKC RKIP Raf RKIP GRK2 G RKIP NIK TAK1 IKKα IKKβ NF-κB MAPK (1) RKIP Raf [7,16] (2) RKIP Raf PAK [17]

4 34 RKIP Raf-1 GRK-2 NF-κB (NIK TAK1 IKKα IKKβ) RKIP RKIP 4 RKIP (metastasis) [21] (metastasis suppressor gene, MSG) [22], [21,23] Keller [11] RKIP RKIP mrna Gleason score RKIP RKIP RKIP [10] Fu [10] RKIP RKIP RKIP RKIP RKIP RKIP RKIP [10] RKIP [24] RKIP RKIP RKIP RKIP [25] [26] RKIP RKIP RKIP Zhu [27] RKIP MDCK(Madin-Darby canine kidney) RKIP locostatin locostatin RKIP RKIP Raf-1 sirna RKIP RKIP locostatin MDCK RKIP RKIP RKIP RKIP 5 RKIP RKIP [28] RKIP RKIP RKIP RKIP RKIP Jazirehi [29] NHL(non- Hodgkin s lymphoma ) Rituximab RKIP ERK1/2 AP-1 Bcl-xL NHL 6 RKIP RKIP Zhang [30] RKIP β Yamazaki [31] RKIP Schuierer [32] RKIP NF-κB Raf- 1/MEK/ERK RKIP

5 Raf (RKIP) 35 7 RKIP RKIP [33] RKIP RKIP (hippocampal cholinergic neurostimulating peptide HCNP) HCNP RKIP N- HCNP RKIP HCNP (Alzheimer s disease AD) [34] RKIP HCNP [35] [36] RKIP [37] RKIP PKC (diabetic nephropathy) [38] RKIP RKIP PKC [34,38] 8 RKIP RKIP Raf/MEK/ERK G NF-κB RKIP RKIP RKIP RKIP [1] Bernier I, Jolles P. Purification and characterization of a basic 23 kda cytosolic protein from bovine brain. Biochim Biophys Acta, 1984, 790(2): [2] Bernier I, Tresca J P, Jolles P. Ligand-binding studies with a 23kDa protein purified from bovine brain cytosol. Biochim Biophys Acta, 1986, 871(1): [3] Trakul N, Rosner M R. Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein. Cell Res, 2005, 15(1): [4] Chautard H, Jacquet M, Schoentgen F, et al. Tfs1p, a member of the PEBP family, inhibits the ira2p but not the ira1p Ras GTPase-activating protein in Saccharomyces cerevisiae. Eukaryot Cell, 2004, 3(2): [5] Gems D, Maizels R M. An abundant trans-spliced mrna from Toxocara canis infective larvae encodes a 26-kDa protein with homology to phosphatidylethanolamine-binding proteins. J Biol Chem, 1995, 270(31): [6] Pikielny C W, Hasan G, Rouyer F, et al. Members of a family of Drosophila putative odorant-binding proteins are expressed in different subsets of olfactory hairs. Neuron, 1994, 12(1): [7] Yeung K, Seitz T, Li S, et al. Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature, 1999, 401(6749): [8] Lorenz K, Lohse M J, Quitterer U. Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature, 2003, 426 (6966): [9] Yeung K C, Rose D W, Dhillon A S, et al. Raf kinase inhibitor protein interacts with NF-κB-inducing kinase and TAK1 and inhibits NF-κB activation. Mol Cell Biol, 2001, 21(21): [10] Fu Z, Smith P C, Zhang L, et al. Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. J Natl Cancer Inst, 2003, 95(12): [11] Keller E T, Fu Z, Brennan M. The biology of a prostate cancer metastasis suppressor protein: Raf kinase inhibitor protein. J Cell Bichem, 2005, 94 (2): [12] Hickox D M, Gibbs G, Morrison J R, et al. Identification of a novel testis-specific member of the phosphatidylethanolamine binding protein family, pebp-2. Biol Reprod, 2002, 67 (3): [13] Wang X J, Li N, Liu B, et al. A nove human phosphatidylethanolamine-binding protein resists tumor necrosis factor - induced apoptosis by inhibiting mitogen-activated protein kinase pathway activation and phosphatidylethanolamine externalization. J Biol Chem, 2004, 279(14): [14] Serre L, Vallee B, Bureaud N, et al. Crystal structure of the phosphatidylethanolamine-binding protein from bovine brain: a novel structural class of phospholipid-binding proteins. Structure, 1998, 6(10): [15] Vallee B S, Tauc P, Brochon J C, et al. Behaviour of bovine phosphatidylethanolamine-binding protein with model membranes. Evidence of affinity for negatively charged membranes. Eur J Biochem, 2001, 268(22): [16] Yeung K, Janosch P, McFerran B, et al. Mechanism of sup-

6 36 pression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol, 2000, 20(9): [17] Trakul N, Menard R E, Schade G R, et al. Raf kinase inhibitory protein regulates Raf-1 but not B-Raf kinase activation. J Biol Chem, 2005, 280 (26): [18] Park S, Yeung M L, Yeung K C, et al. RKIP downregulates B-Raf kinase activity in melanoma cancer cells. Oncogene, 2005, 24 (21): [19] Corbit K C, Trakul N, Eves E M, et al. Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. J Biol Chem, 2003, 278 (15): [20] Kroslak T, Koch T, Kahl E, et al. Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G protein-dependent signaling. J Biol Chem, 2001, 276(43): [21] Yoshida B A, Sokoloff M M, Welch D R, et al. Metastasissuppressor genes: a review and perspective on an emerging field. J Natl Cancer Inst, 2000, 92(21): [22] Welch D R, Rinker-Schaeffer C W. What defines a useful marker of metastasis in human cancer? J Natl Cancer Inst, 1999, 91(16): [23] Steeg P S, Bevilacqua G, Kopper L, et al. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst, 1988, 80(3): [24] Fu Z, Kitagawa Y, Keller E T, et al. Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. Prostate, 2006, 66(3): [25] Hagan S, Al-Mulla F, Mallon E, et al. Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis. Clin Cancer Res, 2005, 11(20): [26] Schuierer M M, Bataille F, Hagan S, et al. Reduction in Raf kinase inhibitor protein expression is associated with increased Ras-extracellular signal-regulated kinase signaling in melanoma cell lines. Cancer Res, 2004, 64(15): [27] Zhu S, McHenry K T, Lane W S, et al. A chemical inhibitor reveals the role of Raf kinase inhibitor protein in cell migration.chem Biol, 2005, 12(9): [28] Chatterjee D, Bai Y, Yeung K C, et al. RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem, 2004, 279(17): [29] Jazirehi A R, Vega M I, Chatterjee D, et al. Inhibition of the Raf-MEK1/2-ERK1/2 signaling pathway, Bcl-xL downregulation,and chemosensitization of non-hodgkin s lymphoma B cells by rituximab. Cancer Res, 2004, 64(19): [30] Zhang L, Fu Z, Simeone D M, et al. Raf kinase inhibitory protein inhibits β-cell proliferation. Surgery, 2004, 136(3): [31] Yamazaki T, Nakano H, Tsuchida S, et al. Differentiation induction of human keratinocytes by phosphatidylethanolamine-binding protein. J Biol Chem, 2004, 279(31): [32] Schuierer M M, Heilmeier U, Langmann T, et al. Induction of Raf kinase inhibitor protein contributes to macrophage differentiation. Biochem Biophys Res Commun, 2006, 342 (4): [33] Hengst U, Albrecht H, Hess D, et al. The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors. J Biol Chem, 2001, 276(1): [34] Keller E T, Zheng F, Brennan M, et al. The role of Raf kinase inhibitor protein (RKIP) in health and disease. Biochem Pharmacol, 2004, 68(6): [35] Moore C, Perry A C, Love S, et al. Sequence analysis and immunolocalisation of phosphatidylethanolamine binding protein (PBP) in human brain tissue. Brain Res Mol Brain Res, 1996, 37(1/2): [36] Goumon Y, Angelone T, Schoentgen F, et al. The hippocampal cholinergic neurostimulating peptide, the N terminal fragment of the secreted phosphatidylethanolamine-binding protein, possess a new biological activity on cardiac physiology. J Biol Chem, 2004, 279(13): [37] Frayne J, McMillen A, Love S, et al. Expression of phosphatidylethanolamine-binding protein in the male reproductive tract: immunolocalisation and expression in prepubertal and adult rat testes and epididymides. Mol Rep Dev, 1998, 49(4): [38] Thongboonkerd V, Klein J B. Practical bioinformatics for proteomics. Contrib Nephrol, 2004, 141: 79-92

Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein

MINIREVIEW Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein Nicholas TRAKUL, Marsha R. ROSNER * Ben May Institute for Cancer Research, University of Chicago, 5841 S. Maryland