Growth hormone receptor targeting to lipid rafts requires extracellular subdomain 2

Yang, N, Jiang, J, Deng, L. Q., Waters, M. J., Wang, X. D. and Frank, S. J. (2010) Growth hormone receptor targeting to lipid rafts requires extracellular subdomain 2. Biochemical and Biophysical Research Communications, 391 1: 414-418. doi:10.1016/j.bbrc.2009.11.072


Author Yang, N
Jiang, J
Deng, L. Q.
Waters, M. J.
Wang, X. D.
Frank, S. J.
Title Growth hormone receptor targeting to lipid rafts requires extracellular subdomain 2
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
Publication date 2010-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2009.11.072
Volume 391
Issue 1
Start page 414
End page 418
Total pages 5
Editor W. Baumeister
Place of publication San Deigo, California, U.S.A.
Publisher Academic Press
Collection year 2010
Language eng
Subject C1
920106 Endocrine Organs and Diseases (excl. Diabetes)
060111 Signal Transduction
Abstract GH receptor (GHR) is a single membrane-spanning glycoprotein dimer that binds GH in its extracellular domain (ECD). GH activates the GHR intracellular domain (ICD)-associated tyrosine kinase, JAK2, which causes intracellular signaling. We previously found that plasma membrane (PM)-associated GHR was dramatically enriched in the lipid raft (LR) component of the membrane and that localization of GHR within PM regions may regulate GH signaling by influencing the profile of pathway activation. In this study, we examined determinants of LR localization of the GHR using a reconstitution system which lacks endogenous JAK2 and GHR. By non-detergent extraction and multistep fractionation, we found that GHR was highly enriched in the LR fraction independent of JAK2 expression. Various GHR mutants were examined in transfectants harboring JAK2. LR concentration was observed for a GHR in which the native transmembrane domain (TMD) is replaced by that of the unrelated LDL receptor and for a GHR that lacks its ICD. Thus, LR association requires neither the TMD nor the ICD. Similarly, a GHR that lacks the ECD, except for the membrane-proximal ECD stem region, was only minimally LR-concentrated. Mutants with internal stem deletions in the context of the full-length receptor were LR-concentrated similar to the wild-type. A GHR lacking ECD subdomain 1 reached the PM and was LR-concentrated, while one lacking ECD subdomain 2, also reached the PM, but was not LR-concentrated. These data suggest LR targeting resides in ECD subdomain 2, a region relatively uninvolved in GH binding.
Keyword Growth hormone receptor
Lipid raft
Determinant
JAK2 TYROSINE KINASE
TRANSMEMBRANE DOMAIN
CYTOPLASMIC DOMAIN
INTERFERON-GAMMA
GH
MEMBRANE
ACTIVATION
PHOSPHORYLATION
LOCALIZATION
CELLS
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 31 Jan 2010, 00:05:53 EST