Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation

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Standard

Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation. / Chhabra, Yash; Seiffert, Pernille; Gormal, Rachel S.; Vullings, Manon; Lee, Christine Mei Mei; Wallis, Tristan P.; Dehkhoda, Farhad; Indrakumar, Sowmya; Jacobsen, Nina L.; Lindorff-Larsen, Kresten; Durisic, Nela; Waters, Michael J.; Meunier, Frédéric A.; Kragelund, Birthe B.; Brooks, Andrew J.

I: Cell Reports, Bind 42, Nr. 5, 112490, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Chhabra, Y, Seiffert, P, Gormal, RS, Vullings, M, Lee, CMM, Wallis, TP, Dehkhoda, F, Indrakumar, S, Jacobsen, NL, Lindorff-Larsen, K, Durisic, N, Waters, MJ, Meunier, FA, Kragelund, BB & Brooks, AJ 2023, 'Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation', Cell Reports, bind 42, nr. 5, 112490. https://doi.org/10.1016/j.celrep.2023.112490

APA

Chhabra, Y., Seiffert, P., Gormal, R. S., Vullings, M., Lee, C. M. M., Wallis, T. P., Dehkhoda, F., Indrakumar, S., Jacobsen, N. L., Lindorff-Larsen, K., Durisic, N., Waters, M. J., Meunier, F. A., Kragelund, B. B., & Brooks, A. J. (2023). Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation. Cell Reports, 42(5), [112490]. https://doi.org/10.1016/j.celrep.2023.112490

Vancouver

Chhabra Y, Seiffert P, Gormal RS, Vullings M, Lee CMM, Wallis TP o.a. Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation. Cell Reports. 2023;42(5). 112490. https://doi.org/10.1016/j.celrep.2023.112490

Author

Chhabra, Yash ; Seiffert, Pernille ; Gormal, Rachel S. ; Vullings, Manon ; Lee, Christine Mei Mei ; Wallis, Tristan P. ; Dehkhoda, Farhad ; Indrakumar, Sowmya ; Jacobsen, Nina L. ; Lindorff-Larsen, Kresten ; Durisic, Nela ; Waters, Michael J. ; Meunier, Frédéric A. ; Kragelund, Birthe B. ; Brooks, Andrew J. / Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation. I: Cell Reports. 2023 ; Bind 42, Nr. 5.

Bibtex

@article{b2298dbda8104f2788b70daf6f4073e7,
title = "Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation",
abstract = "Growth hormone (GH) acts via JAK2 and LYN to regulate growth, metabolism, and neural function. However, the relationship between these tyrosine kinases remains enigmatic. Through an interdisciplinary approach combining cell biology, structural biology, computation, and single-particle tracking on live cells, we find overlapping LYN and JAK2 Box1-Box2-binding regions in GH receptor (GHR). Our data implicate direct competition between JAK2 and LYN for GHR binding and imply divergent signaling profiles. We show that GHR exhibits distinct mobility states within the cell membrane and that activation of LYN by GH mediates GHR immobilization, thereby initiating its nanoclustering in the membrane. Importantly, we observe that LYN mediates cytokine receptor degradation, thereby controlling receptor turnover and activity, and this applies to related cytokine receptors. Our study offers insight into the molecular interactions of LYN with GHR and highlights important functions for LYN in regulating GHR nanoclustering, signaling, and degradation, traits broadly relevant to many cytokine receptors.",
keywords = "box1-box2, CP: Molecular biology, cytokine receptor, ERK1/2, IDPs, integrative structural biology, intrinsically disordered proteins, JAK2, LYN, nanoclusters, NMR, nuclear magnetic resonance, super-resolution microscopy",
author = "Yash Chhabra and Pernille Seiffert and Gormal, {Rachel S.} and Manon Vullings and Lee, {Christine Mei Mei} and Wallis, {Tristan P.} and Farhad Dehkhoda and Sowmya Indrakumar and Jacobsen, {Nina L.} and Kresten Lindorff-Larsen and Nela Durisic and Waters, {Michael J.} and Meunier, {Fr{\'e}d{\'e}ric A.} and Kragelund, {Birthe B.} and Brooks, {Andrew J.}",
note = "Publisher Copyright: {\textcopyright} 2023",
year = "2023",
doi = "10.1016/j.celrep.2023.112490",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation

AU - Chhabra, Yash

AU - Seiffert, Pernille

AU - Gormal, Rachel S.

AU - Vullings, Manon

AU - Lee, Christine Mei Mei

AU - Wallis, Tristan P.

AU - Dehkhoda, Farhad

AU - Indrakumar, Sowmya

AU - Jacobsen, Nina L.

AU - Lindorff-Larsen, Kresten

AU - Durisic, Nela

AU - Waters, Michael J.

AU - Meunier, Frédéric A.

AU - Kragelund, Birthe B.

AU - Brooks, Andrew J.

N1 - Publisher Copyright: © 2023

PY - 2023

Y1 - 2023

N2 - Growth hormone (GH) acts via JAK2 and LYN to regulate growth, metabolism, and neural function. However, the relationship between these tyrosine kinases remains enigmatic. Through an interdisciplinary approach combining cell biology, structural biology, computation, and single-particle tracking on live cells, we find overlapping LYN and JAK2 Box1-Box2-binding regions in GH receptor (GHR). Our data implicate direct competition between JAK2 and LYN for GHR binding and imply divergent signaling profiles. We show that GHR exhibits distinct mobility states within the cell membrane and that activation of LYN by GH mediates GHR immobilization, thereby initiating its nanoclustering in the membrane. Importantly, we observe that LYN mediates cytokine receptor degradation, thereby controlling receptor turnover and activity, and this applies to related cytokine receptors. Our study offers insight into the molecular interactions of LYN with GHR and highlights important functions for LYN in regulating GHR nanoclustering, signaling, and degradation, traits broadly relevant to many cytokine receptors.

AB - Growth hormone (GH) acts via JAK2 and LYN to regulate growth, metabolism, and neural function. However, the relationship between these tyrosine kinases remains enigmatic. Through an interdisciplinary approach combining cell biology, structural biology, computation, and single-particle tracking on live cells, we find overlapping LYN and JAK2 Box1-Box2-binding regions in GH receptor (GHR). Our data implicate direct competition between JAK2 and LYN for GHR binding and imply divergent signaling profiles. We show that GHR exhibits distinct mobility states within the cell membrane and that activation of LYN by GH mediates GHR immobilization, thereby initiating its nanoclustering in the membrane. Importantly, we observe that LYN mediates cytokine receptor degradation, thereby controlling receptor turnover and activity, and this applies to related cytokine receptors. Our study offers insight into the molecular interactions of LYN with GHR and highlights important functions for LYN in regulating GHR nanoclustering, signaling, and degradation, traits broadly relevant to many cytokine receptors.

KW - box1-box2

KW - CP: Molecular biology

KW - cytokine receptor

KW - ERK1/2

KW - IDPs

KW - integrative structural biology

KW - intrinsically disordered proteins

KW - JAK2

KW - LYN

KW - nanoclusters

KW - NMR

KW - nuclear magnetic resonance

KW - super-resolution microscopy

U2 - 10.1016/j.celrep.2023.112490

DO - 10.1016/j.celrep.2023.112490

M3 - Journal article

C2 - 37163374

AN - SCOPUS:85158001066

VL - 42

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 5

M1 - 112490

ER -

ID: 347294993