Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function
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Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function. / Lobie, P E; Allevato, G; Norstedt, G; Billestrup, N; Nielsen, Jens Høiriis.
I: The Journal of Biological Chemistry, Bind 270, Nr. 37, 15.09.1995, s. 21745-50.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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T1 - Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function
AU - Lobie, P E
AU - Allevato, G
AU - Norstedt, G
AU - Billestrup, N
AU - Nielsen, Jens Høiriis
PY - 1995/9/15
Y1 - 1995/9/15
N2 - We have examined the involvement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor in the cellular response to GH. Stable Chinese hamster ovary (CHO) cell clones expressing a receptor with tyrosine residues at position 333 and 338 of the receptor substituted for phenylalanine (CHO-GHR1-638 Y333F, Y338F) were generated by cDNA transfection. Compared with the wild type receptor the Y333F,Y338F mutant possessed normal high affinity ligand binding, hormone internalization, and ligand-induced receptor down-regulation. GH activation of mitogen-associated protein kinase was also similar in CHO clones expressing similar wild type and Y333F,Y338F receptor number. However, two GH-regulated cellular events (lipogenesis, and protein synthesis) were deficient in the tyrosine substituted receptor. In contrast, transcriptional regulation by GH (as evidenced by chloramphenicol acetyltransferase cDNA expression driven by the GH-responsive region of the SPI 2.1 gene) was not affected by Y333F,Y338F substitution. Thus we provide the first experimental evidence that specific tyrosine residues of the GH receptor are required for selected cellular responses to GH.
AB - We have examined the involvement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor in the cellular response to GH. Stable Chinese hamster ovary (CHO) cell clones expressing a receptor with tyrosine residues at position 333 and 338 of the receptor substituted for phenylalanine (CHO-GHR1-638 Y333F, Y338F) were generated by cDNA transfection. Compared with the wild type receptor the Y333F,Y338F mutant possessed normal high affinity ligand binding, hormone internalization, and ligand-induced receptor down-regulation. GH activation of mitogen-associated protein kinase was also similar in CHO clones expressing similar wild type and Y333F,Y338F receptor number. However, two GH-regulated cellular events (lipogenesis, and protein synthesis) were deficient in the tyrosine substituted receptor. In contrast, transcriptional regulation by GH (as evidenced by chloramphenicol acetyltransferase cDNA expression driven by the GH-responsive region of the SPI 2.1 gene) was not affected by Y333F,Y338F substitution. Thus we provide the first experimental evidence that specific tyrosine residues of the GH receptor are required for selected cellular responses to GH.
KW - Amino Acid Sequence
KW - Animals
KW - CHO Cells
KW - Calcium-Calmodulin-Dependent Protein Kinases
KW - Chloramphenicol O-Acetyltransferase
KW - Cricetinae
KW - Down-Regulation
KW - Growth Hormone
KW - Humans
KW - Kinetics
KW - Leucine
KW - Point Mutation
KW - Protein Biosynthesis
KW - Rats
KW - Receptors, Somatotropin
KW - Recombinant Proteins
KW - Transfection
KW - Tyrosine
M3 - Journal article
C2 - 7665593
VL - 270
SP - 21745
EP - 21750
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 37
ER -
ID: 47973103