Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins

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Standard

Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins. / Hansen, J A; Lindberg, K; Hilton, D J; Nielsen, Jens Høiriis; Billestrup, N.

I: Molecular endocrinology (Baltimore, Md.), Bind 13, Nr. 11, 11.1999, s. 1832-43.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Hansen, JA, Lindberg, K, Hilton, DJ, Nielsen, JH & Billestrup, N 1999, 'Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins', Molecular endocrinology (Baltimore, Md.), bind 13, nr. 11, s. 1832-43.

APA

Hansen, J. A., Lindberg, K., Hilton, D. J., Nielsen, J. H., & Billestrup, N. (1999). Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins. Molecular endocrinology (Baltimore, Md.), 13(11), 1832-43.

Vancouver

Hansen JA, Lindberg K, Hilton DJ, Nielsen JH, Billestrup N. Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins. Molecular endocrinology (Baltimore, Md.). 1999 nov;13(11):1832-43.

Author

Hansen, J A ; Lindberg, K ; Hilton, D J ; Nielsen, Jens Høiriis ; Billestrup, N. / Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins. I: Molecular endocrinology (Baltimore, Md.). 1999 ; Bind 13, Nr. 11. s. 1832-43.

Bibtex

@article{96986cb9584c4978a16031f5380d1264,
title = "Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins",
abstract = "In this study we have investigated the role of suppressor of cytokine signaling (SOCS) proteins in GH receptor-mediated signaling. GH-induced transcription was inhibited by SOCS-1 and SOCS-3, while SOCS-2 and cytokine inducible SH2-containing protein (CIS) had no effect By using chimeric SOCS proteins it was found that the ability of SOCS proteins to inhibit GH-mediated transcription was located in the amino-terminal 40-80 amino acids. In SOCS-3, 46 amino acids C-terminal to the SH2 domain were required for the inhibitory activity, while a truncated SOCS-1 having only 2 amino acids C-terminal to the SH2 domain was able to inhibit GH-mediated transcription. Both SOCS-1 and SOCS-3 were able to inhibit GH-induced STAT5 (signal transducer and activator of transcription) activation. SOCS-1 inhibited the tyrosine kinase activity of Janus kinase 2 (JAK2) directly, while SOCS-3 only inhibited JAK2 when stimulated by the GH receptor. All four SOCS proteins were able to bind to a tyrosine-phosphorylated glutathione-S-transferase-GH receptor fusion protein, and SOCS-3 required the same 46 C-terminal amino acids for GH receptor binding as it did for inhibition of GH-mediated transcription and STAT5 activation. These data suggest that SOCS-1 and -3 can suppress GH-induced transcriptional activity, presumably by inhibiting the kinase activity of JAK2 either directly in the case of SOCS-1 or via binding to the tyrosine-phosphorylated GH receptor in the case of SOCS-3.",
keywords = "Amino Acid Sequence, Animals, CHO Cells, Carrier Proteins, Cricetinae, DNA-Binding Proteins, Growth Hormone, Janus Kinase 2, Milk Proteins, Molecular Sequence Data, Phosphorylation, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Receptors, Somatotropin, STAT5 Transcription Factor, Signal Transduction, Trans-Activators, Transcription, Genetic, src Homology Domains",
author = "Hansen, {J A} and K Lindberg and Hilton, {D J} and Nielsen, {Jens H{\o}iriis} and N Billestrup",
year = "1999",
month = "11",
language = "English",
volume = "13",
pages = "1832--43",
journal = "Molecular Endocrinology",
issn = "0888-8809",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Mechanism of inhibition of growth hormone receptor signaling by suppressor of cytokine signaling proteins

AU - Hansen, J A

AU - Lindberg, K

AU - Hilton, D J

AU - Nielsen, Jens Høiriis

AU - Billestrup, N

PY - 1999/11

Y1 - 1999/11

N2 - In this study we have investigated the role of suppressor of cytokine signaling (SOCS) proteins in GH receptor-mediated signaling. GH-induced transcription was inhibited by SOCS-1 and SOCS-3, while SOCS-2 and cytokine inducible SH2-containing protein (CIS) had no effect By using chimeric SOCS proteins it was found that the ability of SOCS proteins to inhibit GH-mediated transcription was located in the amino-terminal 40-80 amino acids. In SOCS-3, 46 amino acids C-terminal to the SH2 domain were required for the inhibitory activity, while a truncated SOCS-1 having only 2 amino acids C-terminal to the SH2 domain was able to inhibit GH-mediated transcription. Both SOCS-1 and SOCS-3 were able to inhibit GH-induced STAT5 (signal transducer and activator of transcription) activation. SOCS-1 inhibited the tyrosine kinase activity of Janus kinase 2 (JAK2) directly, while SOCS-3 only inhibited JAK2 when stimulated by the GH receptor. All four SOCS proteins were able to bind to a tyrosine-phosphorylated glutathione-S-transferase-GH receptor fusion protein, and SOCS-3 required the same 46 C-terminal amino acids for GH receptor binding as it did for inhibition of GH-mediated transcription and STAT5 activation. These data suggest that SOCS-1 and -3 can suppress GH-induced transcriptional activity, presumably by inhibiting the kinase activity of JAK2 either directly in the case of SOCS-1 or via binding to the tyrosine-phosphorylated GH receptor in the case of SOCS-3.

AB - In this study we have investigated the role of suppressor of cytokine signaling (SOCS) proteins in GH receptor-mediated signaling. GH-induced transcription was inhibited by SOCS-1 and SOCS-3, while SOCS-2 and cytokine inducible SH2-containing protein (CIS) had no effect By using chimeric SOCS proteins it was found that the ability of SOCS proteins to inhibit GH-mediated transcription was located in the amino-terminal 40-80 amino acids. In SOCS-3, 46 amino acids C-terminal to the SH2 domain were required for the inhibitory activity, while a truncated SOCS-1 having only 2 amino acids C-terminal to the SH2 domain was able to inhibit GH-mediated transcription. Both SOCS-1 and SOCS-3 were able to inhibit GH-induced STAT5 (signal transducer and activator of transcription) activation. SOCS-1 inhibited the tyrosine kinase activity of Janus kinase 2 (JAK2) directly, while SOCS-3 only inhibited JAK2 when stimulated by the GH receptor. All four SOCS proteins were able to bind to a tyrosine-phosphorylated glutathione-S-transferase-GH receptor fusion protein, and SOCS-3 required the same 46 C-terminal amino acids for GH receptor binding as it did for inhibition of GH-mediated transcription and STAT5 activation. These data suggest that SOCS-1 and -3 can suppress GH-induced transcriptional activity, presumably by inhibiting the kinase activity of JAK2 either directly in the case of SOCS-1 or via binding to the tyrosine-phosphorylated GH receptor in the case of SOCS-3.

KW - Amino Acid Sequence

KW - Animals

KW - CHO Cells

KW - Carrier Proteins

KW - Cricetinae

KW - DNA-Binding Proteins

KW - Growth Hormone

KW - Janus Kinase 2

KW - Milk Proteins

KW - Molecular Sequence Data

KW - Phosphorylation

KW - Protein-Tyrosine Kinases

KW - Proteins

KW - Proto-Oncogene Proteins

KW - Receptors, Somatotropin

KW - STAT5 Transcription Factor

KW - Signal Transduction

KW - Trans-Activators

KW - Transcription, Genetic

KW - src Homology Domains

M3 - Journal article

VL - 13

SP - 1832

EP - 1843

JO - Molecular Endocrinology

JF - Molecular Endocrinology

SN - 0888-8809

IS - 11

ER -

ID: 47972582