RhoH is important for positive thymocyte selection and T-cell receptor signaling.

Tatjana Dorn; Ursula Kuhn; Gerd Bungartz; Sebastian Stiller; Martina Bauer; Joachim Ellwart; Thorsten Peters; Karin Scharffetter-Kochanek; Monika Semmrich; Melanie Laschinger; Bernhard Holzmann; Wolfgang E F Klinkert; Per Thor Straten; Tania Køllgaard; Michael Sixt; Cord Brakebusch

doi:10.1182/blood-2006-04-019034

RhoH is important for positive thymocyte selection and T-cell receptor signaling.

Tatjana Dorn, Ursula Kuhn, Gerd Bungartz, Sebastian Stiller, Martina Bauer, Joachim Ellwart, Thorsten Peters, Karin Scharffetter-Kochanek, Monika Semmrich, Melanie Laschinger, Bernhard Holzmann, Wolfgang E F Klinkert, Per Thor Straten, Tania Køllgaard, Michael Sixt, Cord Brakebusch

61 Citations (Scopus)

Abstract

RhoH is a small GTPase expressed only in the hematopoietic system. With the use of mice with targeted disruption of the RhoH gene, we demonstrated that RhoH is crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Furthermore, the differentiation and expansion of DN3 and DN4 thymocytes in vitro were severely impaired. These defects corresponded to defective TCR signaling. Although RhoH is not required for TCR-induced activation of ZAP70 and ZAP70-mediated activation of p38, it is crucial for the tyrosine phosphorylation of LAT, PLCgamma1, and Vav1 and for the activation of Erk and calcium influx. These data suggest that RhoH is important for pre-TCR and TCR signaling because it allows the efficient interaction of ZAP70 with the LAT signalosome, thus regulating thymocyte development.

Original language	English
Journal	Blood
Volume	109
Issue number	6
Pages (from-to)	2346-55
Number of pages	9
ISSN	0006-4971
DOIs	https://doi.org/10.1182/blood-2006-04-019034
Publication status	Published - 2006

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Dorn, T., Kuhn, U., Bungartz, G., Stiller, S., Bauer, M., Ellwart, J., Peters, T., Scharffetter-Kochanek, K., Semmrich, M., Laschinger, M., Holzmann, B., Klinkert, W. E. F., Straten, P. T., Køllgaard, T., Sixt, M., & Brakebusch, C. (2006). RhoH is important for positive thymocyte selection and T-cell receptor signaling. Blood, 109(6), 2346-55. https://doi.org/10.1182/blood-2006-04-019034

Dorn, T, Kuhn, U, Bungartz, G, Stiller, S, Bauer, M, Ellwart, J, Peters, T, Scharffetter-Kochanek, K, Semmrich, M, Laschinger, M, Holzmann, B, Klinkert, WEF, Straten, PT, Køllgaard, T, Sixt, M & Brakebusch, C 2006, 'RhoH is important for positive thymocyte selection and T-cell receptor signaling.', Blood, vol. 109, no. 6, pp. 2346-55. https://doi.org/10.1182/blood-2006-04-019034

@article{93553f90589211dd8d9f000ea68e967b,

title = "RhoH is important for positive thymocyte selection and T-cell receptor signaling.",

abstract = "RhoH is a small GTPase expressed only in the hematopoietic system. With the use of mice with targeted disruption of the RhoH gene, we demonstrated that RhoH is crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Furthermore, the differentiation and expansion of DN3 and DN4 thymocytes in vitro were severely impaired. These defects corresponded to defective TCR signaling. Although RhoH is not required for TCR-induced activation of ZAP70 and ZAP70-mediated activation of p38, it is crucial for the tyrosine phosphorylation of LAT, PLCgamma1, and Vav1 and for the activation of Erk and calcium influx. These data suggest that RhoH is important for pre-TCR and TCR signaling because it allows the efficient interaction of ZAP70 with the LAT signalosome, thus regulating thymocyte development.",

author = "Tatjana Dorn and Ursula Kuhn and Gerd Bungartz and Sebastian Stiller and Martina Bauer and Joachim Ellwart and Thorsten Peters and Karin Scharffetter-Kochanek and Monika Semmrich and Melanie Laschinger and Bernhard Holzmann and Klinkert, {Wolfgang E F} and Straten, {Per Thor} and Tania K{\o}llgaard and Michael Sixt and Cord Brakebusch",

note = "Keywords: Animals; Antigens, CD18; Biological Markers; Calcium; Cell Adhesion; Cell Movement; Cell Proliferation; Cells, Cultured; Hematopoiesis; Mice; Mice, Knockout; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes; Thymus Gland; Transcription Factors; rho GTP-Binding Proteins",

year = "2006",

doi = "10.1182/blood-2006-04-019034",

language = "English",

volume = "109",

pages = "2346--55",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "6",

}

TY - JOUR

T1 - RhoH is important for positive thymocyte selection and T-cell receptor signaling.

AU - Dorn, Tatjana

AU - Kuhn, Ursula

AU - Bungartz, Gerd

AU - Stiller, Sebastian

AU - Bauer, Martina

AU - Ellwart, Joachim

AU - Peters, Thorsten

AU - Scharffetter-Kochanek, Karin

AU - Semmrich, Monika

AU - Laschinger, Melanie

AU - Holzmann, Bernhard

AU - Klinkert, Wolfgang E F

AU - Straten, Per Thor

AU - Køllgaard, Tania

AU - Sixt, Michael

AU - Brakebusch, Cord

N1 - Keywords: Animals; Antigens, CD18; Biological Markers; Calcium; Cell Adhesion; Cell Movement; Cell Proliferation; Cells, Cultured; Hematopoiesis; Mice; Mice, Knockout; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes; Thymus Gland; Transcription Factors; rho GTP-Binding Proteins

PY - 2006

Y1 - 2006

N2 - RhoH is a small GTPase expressed only in the hematopoietic system. With the use of mice with targeted disruption of the RhoH gene, we demonstrated that RhoH is crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Furthermore, the differentiation and expansion of DN3 and DN4 thymocytes in vitro were severely impaired. These defects corresponded to defective TCR signaling. Although RhoH is not required for TCR-induced activation of ZAP70 and ZAP70-mediated activation of p38, it is crucial for the tyrosine phosphorylation of LAT, PLCgamma1, and Vav1 and for the activation of Erk and calcium influx. These data suggest that RhoH is important for pre-TCR and TCR signaling because it allows the efficient interaction of ZAP70 with the LAT signalosome, thus regulating thymocyte development.

AB - RhoH is a small GTPase expressed only in the hematopoietic system. With the use of mice with targeted disruption of the RhoH gene, we demonstrated that RhoH is crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Furthermore, the differentiation and expansion of DN3 and DN4 thymocytes in vitro were severely impaired. These defects corresponded to defective TCR signaling. Although RhoH is not required for TCR-induced activation of ZAP70 and ZAP70-mediated activation of p38, it is crucial for the tyrosine phosphorylation of LAT, PLCgamma1, and Vav1 and for the activation of Erk and calcium influx. These data suggest that RhoH is important for pre-TCR and TCR signaling because it allows the efficient interaction of ZAP70 with the LAT signalosome, thus regulating thymocyte development.

U2 - 10.1182/blood-2006-04-019034

DO - 10.1182/blood-2006-04-019034

M3 - Journal article

C2 - 17119112

SN - 0006-4971

VL - 109

SP - 2346

EP - 2355

JO - Blood

JF - Blood

IS - 6

ER -

RhoH is important for positive thymocyte selection and T-cell receptor signaling.

Abstract

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