Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase. / VanderKuur, J A; Wang, X; Zhang, L; Campbell, G S; Allevato, G; Billestrup, Nils; Norstedt, G; Carter-Su, C.

I: The Journal of Biological Chemistry, Bind 269, Nr. 34, 26.08.1994, s. 21709-17.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

VanderKuur, JA, Wang, X, Zhang, L, Campbell, GS, Allevato, G, Billestrup, N, Norstedt, G & Carter-Su, C 1994, 'Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase', The Journal of Biological Chemistry, bind 269, nr. 34, s. 21709-17.

APA

VanderKuur, J. A., Wang, X., Zhang, L., Campbell, G. S., Allevato, G., Billestrup, N., Norstedt, G., & Carter-Su, C. (1994). Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase. The Journal of Biological Chemistry, 269(34), 21709-17.

Vancouver

VanderKuur JA, Wang X, Zhang L, Campbell GS, Allevato G, Billestrup N o.a. Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase. The Journal of Biological Chemistry. 1994 aug. 26;269(34):21709-17.

Author

VanderKuur, J A ; Wang, X ; Zhang, L ; Campbell, G S ; Allevato, G ; Billestrup, Nils ; Norstedt, G ; Carter-Su, C. / Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase. I: The Journal of Biological Chemistry. 1994 ; Bind 269, Nr. 34. s. 21709-17.

Bibtex

@article{3344e7e9f40147f7b4e5ae3777281626,
title = "Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase",
abstract = "Growth hormone (GH) has recently been shown to activate the GH receptor (GHR)-associated tyrosine kinase JAK2. In the present study, regions of the GHR required for JAK2 association with GHR were identified. GH-dependent JAK2 association with GHR was detected in Chinese hamster ovary (CHO) cells expressing wild-type GHR (GHR1-638) or GHR truncated at amino acid 454 (GHR1-454) or 380 (GHR1-380). JAK2 did not associate with GHR in cells expressing GHR truncated at amino acid 294 (GHR1-294) or when amino acids 297-311 containing a proline-rich motif were deleted (GHR delta P) or prolines 300, 301, 303, and 305 in the proline-rich motif were mutated to alanines (GHR4P-->A). Cross-linking 125I-human GH to GHR demonstrated that GHR mutants migrated with the appropriate molecular weight, with the exception of GHR4P-->A which migrated as a protein similar in size to GHR1-294. In studies performed in CHO and RIN-5AH cells, the ability of JAK2 to associate with the mutated GHR was found to correlate with GH-dependent activation of JAK2, tyrosyl phosphorylation of GHR (in the case of GHR1-638 and GHR1-454), and the ability of the GHR to copurify with tyrosine kinase activity. In CHO cells expressing mutated GHR, GH-dependent tyrosyl phosphorylation of cellular proteins (p121, p97, p42, and p39) was dependent on the ability to activate JAK2. No proteins showed increased tyrosyl phosphorylation in CHO cells expressing GHR1-294, GHR4P-->A, or GHR delta P. Deletion of the C-terminal half (amino acids 455-638) of the GHR ablated GH-dependent tyrosyl phosphorylation of p97. Taken together, these results provide strong evidence that the N-terminal quarter of the cytoplasmic domain of GHR and within this region, the proline-rich motif, is required for association of JAK2 with GHR and GH-dependent activation of JAK2, and that tyrosines in the N-terminal half of the cytoplasmic domain of the GHR are phosphorylated by JAK2. The finding that a specific interaction with the C-terminal half of GHR appears to be necessary for p97 phosphorylation indicates that while JAK2 activation may be necessary for a full biological response to GH, it appears not to be sufficient.",
keywords = "Animals, Calcium-Calmodulin-Dependent Protein Kinases, DNA Mutational Analysis, Enzyme Activation, Growth Hormone, Humans, Janus Kinase 2, Phosphorylation, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Receptors, Somatotropin, Recombinant Proteins, Sequence Deletion, Signal Transduction, Structure-Activity Relationship",
author = "VanderKuur, {J A} and X Wang and L Zhang and Campbell, {G S} and G Allevato and Nils Billestrup and G Norstedt and C Carter-Su",
year = "1994",
month = aug,
day = "26",
language = "English",
volume = "269",
pages = "21709--17",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "34",

}

RIS

TY - JOUR

T1 - Domains of the growth hormone receptor required for association and activation of JAK2 tyrosine kinase

AU - VanderKuur, J A

AU - Wang, X

AU - Zhang, L

AU - Campbell, G S

AU - Allevato, G

AU - Billestrup, Nils

AU - Norstedt, G

AU - Carter-Su, C

PY - 1994/8/26

Y1 - 1994/8/26

N2 - Growth hormone (GH) has recently been shown to activate the GH receptor (GHR)-associated tyrosine kinase JAK2. In the present study, regions of the GHR required for JAK2 association with GHR were identified. GH-dependent JAK2 association with GHR was detected in Chinese hamster ovary (CHO) cells expressing wild-type GHR (GHR1-638) or GHR truncated at amino acid 454 (GHR1-454) or 380 (GHR1-380). JAK2 did not associate with GHR in cells expressing GHR truncated at amino acid 294 (GHR1-294) or when amino acids 297-311 containing a proline-rich motif were deleted (GHR delta P) or prolines 300, 301, 303, and 305 in the proline-rich motif were mutated to alanines (GHR4P-->A). Cross-linking 125I-human GH to GHR demonstrated that GHR mutants migrated with the appropriate molecular weight, with the exception of GHR4P-->A which migrated as a protein similar in size to GHR1-294. In studies performed in CHO and RIN-5AH cells, the ability of JAK2 to associate with the mutated GHR was found to correlate with GH-dependent activation of JAK2, tyrosyl phosphorylation of GHR (in the case of GHR1-638 and GHR1-454), and the ability of the GHR to copurify with tyrosine kinase activity. In CHO cells expressing mutated GHR, GH-dependent tyrosyl phosphorylation of cellular proteins (p121, p97, p42, and p39) was dependent on the ability to activate JAK2. No proteins showed increased tyrosyl phosphorylation in CHO cells expressing GHR1-294, GHR4P-->A, or GHR delta P. Deletion of the C-terminal half (amino acids 455-638) of the GHR ablated GH-dependent tyrosyl phosphorylation of p97. Taken together, these results provide strong evidence that the N-terminal quarter of the cytoplasmic domain of GHR and within this region, the proline-rich motif, is required for association of JAK2 with GHR and GH-dependent activation of JAK2, and that tyrosines in the N-terminal half of the cytoplasmic domain of the GHR are phosphorylated by JAK2. The finding that a specific interaction with the C-terminal half of GHR appears to be necessary for p97 phosphorylation indicates that while JAK2 activation may be necessary for a full biological response to GH, it appears not to be sufficient.

AB - Growth hormone (GH) has recently been shown to activate the GH receptor (GHR)-associated tyrosine kinase JAK2. In the present study, regions of the GHR required for JAK2 association with GHR were identified. GH-dependent JAK2 association with GHR was detected in Chinese hamster ovary (CHO) cells expressing wild-type GHR (GHR1-638) or GHR truncated at amino acid 454 (GHR1-454) or 380 (GHR1-380). JAK2 did not associate with GHR in cells expressing GHR truncated at amino acid 294 (GHR1-294) or when amino acids 297-311 containing a proline-rich motif were deleted (GHR delta P) or prolines 300, 301, 303, and 305 in the proline-rich motif were mutated to alanines (GHR4P-->A). Cross-linking 125I-human GH to GHR demonstrated that GHR mutants migrated with the appropriate molecular weight, with the exception of GHR4P-->A which migrated as a protein similar in size to GHR1-294. In studies performed in CHO and RIN-5AH cells, the ability of JAK2 to associate with the mutated GHR was found to correlate with GH-dependent activation of JAK2, tyrosyl phosphorylation of GHR (in the case of GHR1-638 and GHR1-454), and the ability of the GHR to copurify with tyrosine kinase activity. In CHO cells expressing mutated GHR, GH-dependent tyrosyl phosphorylation of cellular proteins (p121, p97, p42, and p39) was dependent on the ability to activate JAK2. No proteins showed increased tyrosyl phosphorylation in CHO cells expressing GHR1-294, GHR4P-->A, or GHR delta P. Deletion of the C-terminal half (amino acids 455-638) of the GHR ablated GH-dependent tyrosyl phosphorylation of p97. Taken together, these results provide strong evidence that the N-terminal quarter of the cytoplasmic domain of GHR and within this region, the proline-rich motif, is required for association of JAK2 with GHR and GH-dependent activation of JAK2, and that tyrosines in the N-terminal half of the cytoplasmic domain of the GHR are phosphorylated by JAK2. The finding that a specific interaction with the C-terminal half of GHR appears to be necessary for p97 phosphorylation indicates that while JAK2 activation may be necessary for a full biological response to GH, it appears not to be sufficient.

KW - Animals

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - DNA Mutational Analysis

KW - Enzyme Activation

KW - Growth Hormone

KW - Humans

KW - Janus Kinase 2

KW - Phosphorylation

KW - Protein Binding

KW - Protein-Tyrosine Kinases

KW - Proto-Oncogene Proteins

KW - Receptors, Somatotropin

KW - Recombinant Proteins

KW - Sequence Deletion

KW - Signal Transduction

KW - Structure-Activity Relationship

M3 - Journal article

C2 - 8063815

VL - 269

SP - 21709

EP - 21717

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 34

ER -

ID: 132900525