分子細胞構造学- 病態解析学部門 -
体内には10万キロメートルもの長さの血管が張り巡らされており、私たちの生命を維持しています。そのため、血管の異常は多岐に渡る病気や加齢に伴う老化と密接に関連しています。
病態解析学部門では、“全身を張り巡らす血管が如何に形作られ機能しているのか?” “血管機能の破綻が如何に様々な病気を発症させるのか?”といった疑問を分子レベルで明らかにすることを目的に研究を進めています。
業績
これまで学術誌に報告した論文リストは下記サイトでご覧いただけます。
http://scholar.google.de/citations?user=w1NElGcAAAAJ&hl=en
2020年
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Abdelhakim M., Dohi T., Yamato M., Takada H., Sakai A., Suzuki H., Ema M., Fukuhara S., Ogawa R. A new model for specific visualization of skin graft neoangiogenesis using Flt1-tdsRed BAC transgenic mice. Plast. Reconstr. Surg. In press.
- Fukushima Y., Nishiyama K., Kataoka H., Fruttiger M. Fukuhara S., Nishida K., Mochizuki N., Kurihara H., Nishikawa S., Uemura A. RhoJ integrates attractive and repulsive cues in directional migration of endothelial cells. EMBO J. 39(12):e102930 (2020). doi: 10.15252/embj.2019102930.
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Kobayashi I., Kobayashi-Sun J., Hirakawa Y., Ouchi M., Yasuda K., Kamei H., Fukuhara S., Yamaguchi M. Dual role of Jam3b in early hematopoietic and vascular development. Development 147(1). pii: dev181040 (2020). doi: 10.1242/dev.181040.
2019年
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Rho S., Kobayashi I., Oguri-Nakamura E., Ando K., Fujiwara M., Kamimura N., Hirata H., Iida A., Iwai Y., Mochizuki N., Fukuhara S.(Corresponding author). Rap1b promotes Notch signal-mediated hematopoietic stem cell development by enhancing integrin-mediated cell adhesion. Dev. Cell 49(5):681-696.e6 (2019). doi: 10.1016/j.devcel.2019.03.023.
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*Noishiki C., *Yuge S., Ando K., Wakayama Y., Mochizuki N., Ogawa R., Fukuhara S. (Corresponding author). Live imaging of angiogenesis during cutaneous wound healing in adult zebrafish. Angiogenesis 22(2):341-354 (2019). doi: 10.1007/s10456-018-09660-y. *Equal contribution.
- Simmons S., Sasaki N., Umemoto E., Uchida Y., Fukuhara S., Kitazawa Y., Okudaira M., Inoue A., Tohya K., Aoi K., Aoki J., Mochizuki N., Matsuno K., Takeda K., Miyasaka M., Ishii M. eLife 8. pii: e41239 (2019). doi: 10.7554/eLife.41239.
- Shin M., Nozaki N., Idrizi I., Isogai S., Ogasawara K., Ishida K., Yuge S., Roscoe B., Wolfe S.A., Fukuhara S., Mochizuki N, Deguchi T., Lawson N.D. Valves are a conserved feature of the zebrafish lymphatic system. Dev. Cell 51(3):374-386.e5 (2019). doi: 10.1016/j.devcel.2019.08.019.
- Ando K., Wang W., Peng D. Chiba A., Barske L., Crump J.G., Stainier D.Y.R., Lendahl U., Lagendijk A., Koltowska K., Hogan B.M., Fukuhara S., Mochizuki N., Betsholtz C. Peri-arterial specification of vascular mural cells from naïve mesenchyme requires Notch signaling. Development 146(2). pii: dev165589 (2019). doi: 10.1242/dev.165589.
2017年
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Rho S., Ando K., Fukuhara S. (Corresponding author). Dynamic regulation of vascular permeability by vascular endothelial cadherin-mediated endothelial cell-cell junctions. J. Nippon Med. Sch. 84(4): 148-159 (2017). doi: 10.1272/jnms.84.148.
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Takara K., Eino D., Ando K., Yasuda D., Naito H., Tsukada Y., Iba T., Wakabayashi T., Muramatsu F., Kidoya H., Fukuhara S., Mochizuki N., Ishii S., Kishima H., Takakura N. Lysophosphatidic acid receptor 4 activation augments drug delivery in tumors by tightening endothelial cell-cell contact. Cell Reports 20(9): 2072-2086 (2017). doi: 10.1016/j.celrep.2017.07.080.
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Miura K., Nojiri T., Akitake Y., Ando K., Fukuhara S., Zenitani M., Kimura T., Hino J., Miyazato M., Hosoda H., Kangawa K. CCM2 and PAK4 act downstream of atrial natriuretic peptide signaling to promote cell spreading. Biochem. J. 474: 1897-1918 (2017). doi: 10.1042/BCJ20160841.
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Nakajima H., Yamamoto K., Agarwala S., Terai K., Fukui H., Fukuhara S., Ando K., Miyazaki T, Yokota Y, Schmelzer E., Belting H.-G., Affolter M., Lecaudey V., and Mochizuki N. Flow-dependent endothelial YAP regulation that contributes to vessel maintenance. Dev. Cell 40(6): 523-536 (2017). doi: 10.1016/j.devcel.2017.02.019.
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Chiba A., Watanabe-Takano H., Terai K., Fukui H., Miyazaki T., Uemura M., Hashimoto H., Hibi M., Fukuhara S., and Mochizuki N. Osteocrin, a peptide secreted from the heart and other tissues, contributes to cranial osteogenesis and chondrogenesis in zebrafish. Development 144(2):334-344 (2017). doi: 10.1242/dev.143354.
2016年
- Ando K., Fukuhara S. (Co-corresponding author), Izumi N., Nakajima H., Fukui H., Kelsh R.N., Mochizuki N. Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish. Development 143: 1328-1339 (2016). doi: 10.1242/dev.132654.
- Chavez-Vargas L., Adame-Garcia S.R., Cervantes-Villagrana R.D., Castillo-Kauil A., Bruystens J.G.H., Fukuhara S., Taylor S.S., Mochizuki N., Reyes-Cruz G., Vazquez-Prado J. Protein kinase A (PKA) Type I interacts with P-Rex1, a Rac guanine nucleotide exchange factor: Effect on PKA localization and P-Rex1 signaling. J. Biol. Chem. 291: 6182-6199 (2016). doi: 10.1074/jbc.M115.712216
2015年
- Wakayama Y., Fukuhara S. (Corresponding author), Ando K., Matsuda M., Mochizuki N. Cdc42 mediates Bmp-induced sprouting angiogenesis through Fmnl3-driven assembly of endothelial filopodia in zebrafish. Dev. Cell 32: 109-122 (2015). doi: 10.1016/j.devcel.2014.11.024.
- Kashiwada T., Fukuhara S. (Co-corresponding author), Terai K., Tanaka T., Wakayama Y., Ando K., Nakajima H., Fukui H., Yuge S., Saito Y., Gemma A., Mochizuki N. β-Catenin-dependent transcription is central to Bmp-mediated formation of venous vessels. Development 142: 497-509 (2015). doi: 10.1242/dev.115576.
- Fukuhara S., Fukui H., Wakayama Y., Ando K., Nakajima H., Mochizuki N. Looking back and moving forward: Recent advances in understanding of cardiovascular development by imaging of zebrafish. Dev. Growth Differ. 57: 333-340 (2015). doi: 10.1111/dgd.12210.
- Yokota Y., Nakajima H., Wakayama Y. Muto A., Kawakami K. Fukuhara S., Mochizuki N. Endothelial Ca2+ oscillations reflect VEGFR signaling-regulated angiogenic capacity in vivo. eLife 4 : e08817 (2015). doi: 10.7554/eLife.08817.
- Kim J.-D., Park K.-E., Ishida J., Kako K., Hamada J., Kani S., Takeuchi M., Namiki K., Fukui H., Fukuhara S., Hibi M., Kobayashi M., Kanaho Y., Kasuya Y., Mochizuki N., Fukamizu A. PRMT8 as a phospholipase maintains dendrite formation of Purkinje cells. Science Advances 1: e1500615 (2015). doi: 10.1126/sciadv.1500615.
- Sugihara K., Nishiyama K., Fukuhara S., Uemura A., Arima S., Kobayashi R., Kohn-Luque A., Mochizuki N., Suda T., Ogawa H., Kurihara H. Autonomy and non-autonomy of angiogenic cell movements revealed by experiment-driven mathematical modeling. Cell Reports 13: 1814-1827 (2015). doi: 10.1016/j.celrep.2015.10.051.
- Hongu T., Funakoshi Y., Fukuhara S., Suzuki T., Sakimoto S., Takakura N., Ema M., Takahashi S., Itoh S., Kato M., Hasegawa H., Mochizuki N., Kanaho Y. Arf6 regulates tumor angiogenesis and growth through HGF-induced endothelial β1 integrin recycling. Nat. Commun. 6: 6925 (2015). doi: 10.1038/ncomms8925.
- Vanhollebeke B., Stone O., Bostaille N., Cho C., Zhou Y., Maquet E., Gauquier A., Cabochette P., Fukuhara S., Mochizuki N., Nathans J., Stainier D.Y.R. Tip cell specific requirement for an atypical Gpr124 and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis. eLife 4 : e06489 (2015). doi: 10.7554/eLife.06489.
- Mikelis C.M., Simaan M., Ando K., Fukuhara S., Sakurai A., Amornphimoltham P., Masedunskas A., Weigert R., Chavakis T., Adams R., Offermanns S., Mochizuki N., Zheng Y., Gutkind J.S. RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock. Nat. Commun. 6: 6725 (2015). doi: 10.1038/ncomms7725.
2014年
- Fukuhara S. (Co-corresponding author), Zhang J., Yuge S., Ando K., Wakayama Y., Sakaue-Sawano A., Miyawaki A., Mochizuki N. Visualizing the cell-cycle progression of endothelial cells in zebrafish. Dev. Biol. 393: 10-23 (2014).
- Fukui H., Terai K., Nakajima H., Chiba A., Fukuhara S., Mochizuki N. S1P-Yap1 signaling regulates endoderm formation required for cardiac precursor cell migration in zebrafish. Dev. Cell 31: 128-136 (2014).
- Odagiri H., Kadomatsu T., Endo M., Masuda T., Morioka M.S., Fukuhara S., Miyamoto T., Kobayashi E., Miyata K., Aoi J., Horiguchi H., Nishimura N., Terada K., Yakushiji T., Manabe I., Mochizuki N., Mizuta M., Oike Y. The secreted protein ANGPTL2 promotes metastasis of osteosarcoma cells through integrin α5β1, p38 MAPK, and matrix metalloproteinases. Sci. Signal. 7: ra7 (2014).
- Nakajima K., Shibata Y., Hishikawa Y., Suematsu T., Mori M., Fukuhara S., Koji T., Sawase T., Ikeda T. Coexpression of Ang1 and Tie2 in odontoblasts of mouse developing and mature teeth―a new insight into dentinogenesis. Acta Histochem. Cytochem. 47: 19-25 (2014).
2013年
- Ando K., Fukuhara S. (Co-corresponding author), Moriya T., Obara Y. Nakahata N., Mochizuki N. Rap1 potentiates endothelial cell junctions by spatially controlling myosin II activity and actin organization. J. Cell Biol. 202: 901-916 (2013).
- Kwon H.B., Fukuhara S., Asakawa K., Ando K., Kashiwada T., Kawakami K., Hibi M., Kwon Y.G., Kim K.W., Alitalo K., Mochizuki N. The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signal in zebrafish. Development 140: 4081-4090 (2013).
- Mikelis C.M., Palmby T.R., Simaan M., Li W., Szabo R., Lyons R., Martin D., Yagi H., Fukuhara S., Chikumi H., Galisteo R., Mukouyama Y., Bugge T.H., Gutkind J.S. PDZ-RhoGEF and LARG are essential for embryo development, and provide a link between thrombin and LPA receptors and Rho activation. J. Biol. Chem. 288: 12232-12243 (2013).
2012年
- Fukuhara S. (Co-corresponding author), Simmons S., Kawamura S., Inoue A., Orba Y., Tokudome T., Sunden Y., Arai Y., Moriwaki K., Ishida J., Uemura A, Kiyonari H., Abe T., Fukamizu A., Hirashima M., Sawa H., Aoki J., Ishii M, Mochizuki N. The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice. J. Clin. Invest. 122: 1416-1426 (2012).
- Kusuhara S., Fukushima Y., Fukuhara S., Jakt L.M., Okada M., Shimizu Y., Hata M., Nishida K., Negi A., Hirashima M., Mochizuki N., Nishikawa S., Uemura A. Arhgef15 promotes retinal angiogenesis by mediating VEGF-induced Cdc42 activation and potentiating RhoJ inactivation in endothelial cells. PLoS One 7: e45858 (2012).
- Takenouchi T., Iwamaru Y., Imamura M., Fukuhara S., Sugama S., Sato M., Mochizuki N., Hashimoto M., Yokoyama T., Mohri S., Kitani H. Cytochalasin D enhances the accumulation of a protease-resistant form of prion protein in ScN2a Cells: Involvement of PI3 kinase/Akt signaling pathway. Cell Biol. Int. 36: 1223-1231 (2012).
- Endo M., Nakano M., Kadomatsu T., Fukuhara S., Kuroda H., Mikami S., Hato T., Aoi J., Horiguchi H., Miyata K., Odagiri H., Masuda T., Harada M., Horio H., Hishima T., Nomori H., Ito T., Yamamoto Y., Minami T., Okada S., Takahashi T., Mochizuki N., Iwase H., Oike Y. Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis. Cancer Res. 72: 1784-1794 (2012).
- Makita N., Seki A., Sumitomo N., Chkourko H., Fukuhara S., Watanabe H., Shimizu W., Bezzina C.R., Hasdemir C., Mugishima H., Makiyama T., Baruteau A., Baron E., Horie M., Hagiwara N., Wilde A.A., Probst V., Le Marec H., Roden D.M., Mochizuki N., Schott J.J., Delmar M. A connexin 40 mutation associated with a malignant variant of progressive familial heart block type-1. Circ. Arrhythm. Electrophysiol. 5: 163-172 (2012).
2011年
- Minami M., Koyama T., Wakayama Y., Fukuhara S. (Corresponding author), Mochizuki N. EphrinA/EphA signal facilitates insulin-like growth factor-I-induced myogenic differentiation through suppression of the Ras/extracellular signal-regulated kinase 1/2 cascade in myoblast cell lines. Mol. Biol. Cell 22: 3508-3519 (2011).
- Zhang J., Fukuhara S. (Co-corresponding author), Sako K., Takenouchi T., Kitani H., Kume T., Koh G.Y., Mochizuki N. Angiopoietin-1/Tie2 signal augments basal Notch signal controlling vascular quiescence by inducing delta-like 4 expression through AKT-mediated activation of β-catenin. J. Biol. Chem. 286: 8055-8066 (2011).
2010年
- Noda K., Zhang J., Fukuhara S. (Co-corresponding author), Kunimoto S., Yoshimura M., Mochizuki N. Vascular endothelial-cadherin stabilizes at cell-cell junctions by anchoring to circumferential actin bundles through α- and β-catenins in cyclic AMP-Epac-Rap1 signal-activated endothelial cells. Mol. Biol. Cell 21: 584-596 (2010).
- Fukuhara S. (Corresponding author), Sako K., Noda K., Zhang J., Minami M., Mochizuki N. Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis. Histol. Histopathol. 25: 387-396 (2010).
- Fujimoto C., Ozeki H., Uchijima Y., Suzukawa K., Mitani A., Fukuhara S., Nishiyama K., Kurihara Y., Kondo K., Aburatani H., Kaga K., Yamasoba T., Kurihara H. Establishment of mice expressing EGFP in the placode-derived inner ear sensory cell lineage and FACS-array analysis focused on the regional specificity of the otocyst. J. Comp. Neurol. 518: 4702-4722 (2010).
2009年
- Tabata M., Kadomatsu T., Fukuhara S., Miyata K., Ito Y., Endo M., Urano T., Zhu H.J., Tsukano H., Tazume H., Kaikita K., Miyashita K., Iwawaki T., Shimabukuro M., Sakaguchi K., Ito T., Nakagata N., Yamada T., Katagiri H., Kasuga M., Ando Y., Ogawa H., Mochizuki N., Itoh H., Suda T., Oike Y. Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. Cell Metabolism 10: 178-188 (2009).
- Fukuhara S., Sako K., Noda K., Nagao K., Miura K., Mochizuki N. Tie2 is tied at the cell-cell contacts and to extracellular matrix by Angiopoietin-1. Exp. Mol. Med. 41: 133-139 (2009).
- Sako K., Fukuhara S. (Corresponding author), Minami T., Hamakubo T., Song H., Kodama T., Fukamizu A., Gutkind J.S., Koh G.Y., Mochizuki N. Angiopoietin-1 induces Kruppel-Like Factor 2 expression through a phosphoinositide 3-kinase/AKT-dependent activation of myocyte enhancer factor 2. J. Biol. Chem. 284: 5592-5601 (2009).
2008年
- Fukuhara S. (Co-corresponding author), Sako K., Minami T., Noda K., Kim H.Z., Kodama T., Shibuya M., Takakura N., Koh G.Y., Mochizuki N. Differential function of Tie2 at cell-cell contacts and cell-substratum contacts regulated by angiopoietin-1. Nat. Cell Biol. 10: 513-526 (2008).
- Mukai H., Kikuchi M., Fukuhara S., Kiso Y., Munekata E. Cryptide signaling: amphiphilic peptide-induced exocytosis mechanisms in mast cells. Biochem. Biophys. Res. Commun. 375: 22-26 (2008).
- Makita N., Behr E., Shimizu W., Horie M., Sunami A., Crotti L., Schulze-Bahr E., Fukuhara S., Mochizuki N., Makiyama T., Itoh H., Christiansen M., McKeown P., Miyamoto K., Kamakura S., Tsutsui H., Schwartz P.J., George Jr A. L., Roden D. M. The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome. J. Clin. Invest. 118: 2219-2229 (2008).
- Yasuda N., Miura S., Akazawa H., Tanaka T., Qin Y., Kiya Y., Imaizumi S., Fujino M., Ito K., Zou Y., Ge J., Fukuhara S., Kunimoto S., Mochizuki N., Fukuzaki K., Sato T., Nakaya H., Saku K., Komuro I. Conformational switch of angiotensin II type 1 receptor underlying mechanical stress-induced activation. EMBO Rep. 9: 179-186 (2008).
2007年
- Kamide K., Kokubo Y., Fukuhara S., Hanada H., Yang J., Kada A., Nagura J., Takiuchi S., Horio T., Kawano Y., Okayama A., Tomoike H., Miyata T. Protein Tyrosine Kinase 2β as a Candidate Gene for Hypertension. Pharmacogenet. Genomics. 17: 931-939 (2007).
- Yamaguchi Y., Nagase T., Tomita T., Nakamura K., Fukuhara S., Amano T., Yamamoto H., Ide Y., Suzuki M., Teramoto S., Asano T., Kangawa K., Nakagata N., Ouchi Y., Kurihara H. β-defensin overexpression induces progressive muscle degeneration in mice. Am. J. Physiol. Cell Physiol. 292: C2141-C2149 (2007).
2006年以前の代表的な論文
- Fukuhara S., Sakurai A., Yamagishi A., Sako K., Mochizuki N. Vascular endothelial cadherin-mediated cell-cell adhesion regulated by a small GTPase, Rap1. J. Biochem. Mol. Biol. 39: 132-139 (2006).
- Sakurai A., Fukuhara S., Yamagishi A., Sako K., Kamioka Y., Masuda M., Nakaoka Y., Mochizuki N. MAGI-1 is required for Rap1 activation upon cell-cell contact and for enhancement of vascular endothelial cadherin?mediated cell adhesion. Mol. Biol. Cell 17: 966-976 (2006).
- Somekawa S., Fukuhara S., Nakaoka Y., Fujita H., Saito Y., Mochizuki N. Enhanced functional gap junction neoformation by PKA-dependent and Epac-dependent signals downstream of cAMP in cardiac myocytes. Circ. Res. 97: 655-662 (2005).
- Fujita H., Fukuhara S., Sakurai A., Yamagishi A., Kamioka Y., Nakaoka Y., Masuda M., Mochizuki N. Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied with extension of microtubules on which RapL, a Rap1-associating molecule, localizes. J. Biol. Chem. 280: 5022-5031 (2005).
- Fukuhara S., Sakurai A., Sano H., Yamagishi A., Somekawa S., Takakura N., Saito Y., Kangawa K., Mochizuki N. Cyclic AMP potenciates VE-cadherin?mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway. Mol. Cell. Biol. 25: 136-146 (2005).
- Fukuhara S., Kurihara Y., Arima Y., Yamada N., Kurihara H. Temporal requirement of signaling cascade involving endothelin-1/endothelin receptor type A in branchial arch development. Mech. Dev. 121: 1223-1233 (2004).
- Kamioka Y., Fukuhara S., Sawa H., Nagashima K., Masuda M., Matsuda M., Mochizuki N. A novel dynamin-associating molecule, forming-binding protein 17, induces tubular membrane invaginations and participates in endocytosis. J. Biol. Chem. 279: 40091-40099 (2004).
- Chikumi H., Fukuhara S., Gutkind J.S. Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF and LARG, by tyrosine phosphorylation: Evidence of a role for FAK. J. Biol. Chem. 227: 12463-12467 (2002).
- Fukuhara S., Chikumi H., Gutkind J.S. RGS-containing RhoGEFs: The missing link between transforming G proteins and Rho? Oncogene 20: 1661-1668 (2001).
- Yamaguchi Y., Fukuhara S., Nagase T., Tomita T., Hitomi S., Kimura S., Kurihara H., Ouchi Y. A novel mouse β-defensin, mBD-6, predominantly expressed in skeletal muscle. J. Biol. Chem. 276: 31510-31514 (2001).
- Fukuhara S., Chikumi H., Gutkind J.S. Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G12 family to Rho. FEBS Lett. 485: 183-188 (2000).
- Fukuhara S., Marinissen M.J., Chiariello M., Gutkind J.S. Signaling from G protein-coupled receptors to ERK5/BMK1 involves Gαq and Gα12/13 families of heterotrimeric G proteins: Evidence for the existence of a novel Ras and Rho-independent pathway. J. Biol. Chem. 275: 21730-21736 (2000).
- Chiang Y.J., Kole H.K., Brown K., Naramura M., Fukuhara S., Hu R.-J., Jang I.K., Gutkind J.S., Shevach E., Gu H. Cbl-b regulates the CD28 dependence of T-cell activation. Nature 403: 216-220 (2000).
- Murga C., Fukuhara S., Gutkind J.S. A novel role for phosphatidylinositol 3-kinase β in signaling from G protein-coupled receptors to Akt. J. Biol. Chem. 275: 12069-12073 (2000).
- Pirone D.M., Fukuhara S., Gutkind J.S., Burbelo P.D. SPECs, small binding proteins for Cdc42. J. Biol. Chem. 275: 22650-22656 (2000).
- Fukuhara S., Murga C., Zohar M., Igishi T., Gutkind J.S. A novel PDZ-domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J. Biol. Chem. 274: 5868-5879 (1999).
- Igishi T., Fukuhara S., Patel V., Katz B.-Z., Yamada K.M., Gutkind J.S. Divergent signaling pathways link focal adhesion kinase to mitogen-activated protein kinase cascades: Evidence for a role of paxillin in c-Jun NH2-terminal kinase activation. J. Biol. Chem. 274: 30738-30746 (1999).
- Murga C., Fukuhara S., Gutkind J.S. Novel molecular mediators in the pathway connecting by G protein-coupled receptors to MAP kinases. Trends in Endocrinology and Metabolism 10: 122-127 (1999).