Evidence for insulin-dependent activation of S6 and microtubule-associated protein-2 kinases via a human insulin receptor/v-Ros hybrid

Teri G. Boulton, Jill S. Gregory, Song Muh Jong, Lu Hai Wang, Leland Ellis, Melanie H. Cobb

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The abilities of a series of six mutants of the human insulin receptor, an insulin receptor/v-ros hybrid (IR-ros) and the P68gag-ros transforming protein to stimulate 86 protein kinase have been assessed. Insulin receptor mutants in which either 1 or 2 tyrosine residues have been replaced with phenylalanine (YF1, YF3) have lost some or all of the capacity to mediate the activation of S6 kinase in response to insulin. None of the four mutants that contain deletions (spBam, spBamYF3, iBgl, T-t) elicit an insulin-dependent stimulation of S6 kinase. A previous study of the IRros hybrid receptor demonstrated that it was unable to cause either insulin-stimulated thymidine incorporation or glucose uptake (Ellis, L., Morgan, D. O., Jong, S.-M., Wang, L.-H., Roth, R. A., and Rutter, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5101-5105). In contrast, the IRros chimera appears to mediate the activation of S6 protein kinase by insulin. In further evaluating the biological activities of the IRros hybrid, we have examined its effects on a microtubule-associated protein-2 (MAP2) kinase that is thought to be an early target in the cascade of reactions leading to increased S6 phosphorylation (Sturgill, T. W., Ray, L. B., Erickson, E., and Maller, J. L. (1988) Nature 334, 715-718). We find that the IRros receptor stimulates the MAP2 protein kinase from 3- to 6-fold in insulin-treated cells, conferring more than a 30-fold increase in the insulin sensitivity of MAP2 kinase activation.

Original languageEnglish (US)
Pages (from-to)2713-2719
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number5
StatePublished - 1990

Fingerprint

S 6
Mitogen-Activated Protein Kinase 3
Ribosomal Protein S6 Kinases
Chemical activation
Insulin
Protein Kinases
Insulin Receptor
Phosphorylation
Phenylalanine
Microtubule-Associated Proteins
Thymidine
Insulin Resistance
Bioactivity
human INSR protein
Glucose
Cells
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Evidence for insulin-dependent activation of S6 and microtubule-associated protein-2 kinases via a human insulin receptor/v-Ros hybrid. / Boulton, Teri G.; Gregory, Jill S.; Jong, Song Muh; Wang, Lu Hai; Ellis, Leland; Cobb, Melanie H.

In: Journal of Biological Chemistry, Vol. 265, No. 5, 1990, p. 2713-2719.

Research output: Contribution to journalArticle

Boulton, Teri G. ; Gregory, Jill S. ; Jong, Song Muh ; Wang, Lu Hai ; Ellis, Leland ; Cobb, Melanie H. / Evidence for insulin-dependent activation of S6 and microtubule-associated protein-2 kinases via a human insulin receptor/v-Ros hybrid. In: Journal of Biological Chemistry. 1990 ; Vol. 265, No. 5. pp. 2713-2719.
@article{85338b882b824d728148e98a56b8932e,
title = "Evidence for insulin-dependent activation of S6 and microtubule-associated protein-2 kinases via a human insulin receptor/v-Ros hybrid",
abstract = "The abilities of a series of six mutants of the human insulin receptor, an insulin receptor/v-ros hybrid (IR-ros) and the P68gag-ros transforming protein to stimulate 86 protein kinase have been assessed. Insulin receptor mutants in which either 1 or 2 tyrosine residues have been replaced with phenylalanine (YF1, YF3) have lost some or all of the capacity to mediate the activation of S6 kinase in response to insulin. None of the four mutants that contain deletions (spBam, spBamYF3, iBgl, T-t) elicit an insulin-dependent stimulation of S6 kinase. A previous study of the IRros hybrid receptor demonstrated that it was unable to cause either insulin-stimulated thymidine incorporation or glucose uptake (Ellis, L., Morgan, D. O., Jong, S.-M., Wang, L.-H., Roth, R. A., and Rutter, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5101-5105). In contrast, the IRros chimera appears to mediate the activation of S6 protein kinase by insulin. In further evaluating the biological activities of the IRros hybrid, we have examined its effects on a microtubule-associated protein-2 (MAP2) kinase that is thought to be an early target in the cascade of reactions leading to increased S6 phosphorylation (Sturgill, T. W., Ray, L. B., Erickson, E., and Maller, J. L. (1988) Nature 334, 715-718). We find that the IRros receptor stimulates the MAP2 protein kinase from 3- to 6-fold in insulin-treated cells, conferring more than a 30-fold increase in the insulin sensitivity of MAP2 kinase activation.",
author = "Boulton, {Teri G.} and Gregory, {Jill S.} and Jong, {Song Muh} and Wang, {Lu Hai} and Leland Ellis and Cobb, {Melanie H.}",
year = "1990",
language = "English (US)",
volume = "265",
pages = "2713--2719",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

TY - JOUR

T1 - Evidence for insulin-dependent activation of S6 and microtubule-associated protein-2 kinases via a human insulin receptor/v-Ros hybrid

AU - Boulton, Teri G.

AU - Gregory, Jill S.

AU - Jong, Song Muh

AU - Wang, Lu Hai

AU - Ellis, Leland

AU - Cobb, Melanie H.

PY - 1990

Y1 - 1990

N2 - The abilities of a series of six mutants of the human insulin receptor, an insulin receptor/v-ros hybrid (IR-ros) and the P68gag-ros transforming protein to stimulate 86 protein kinase have been assessed. Insulin receptor mutants in which either 1 or 2 tyrosine residues have been replaced with phenylalanine (YF1, YF3) have lost some or all of the capacity to mediate the activation of S6 kinase in response to insulin. None of the four mutants that contain deletions (spBam, spBamYF3, iBgl, T-t) elicit an insulin-dependent stimulation of S6 kinase. A previous study of the IRros hybrid receptor demonstrated that it was unable to cause either insulin-stimulated thymidine incorporation or glucose uptake (Ellis, L., Morgan, D. O., Jong, S.-M., Wang, L.-H., Roth, R. A., and Rutter, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5101-5105). In contrast, the IRros chimera appears to mediate the activation of S6 protein kinase by insulin. In further evaluating the biological activities of the IRros hybrid, we have examined its effects on a microtubule-associated protein-2 (MAP2) kinase that is thought to be an early target in the cascade of reactions leading to increased S6 phosphorylation (Sturgill, T. W., Ray, L. B., Erickson, E., and Maller, J. L. (1988) Nature 334, 715-718). We find that the IRros receptor stimulates the MAP2 protein kinase from 3- to 6-fold in insulin-treated cells, conferring more than a 30-fold increase in the insulin sensitivity of MAP2 kinase activation.

AB - The abilities of a series of six mutants of the human insulin receptor, an insulin receptor/v-ros hybrid (IR-ros) and the P68gag-ros transforming protein to stimulate 86 protein kinase have been assessed. Insulin receptor mutants in which either 1 or 2 tyrosine residues have been replaced with phenylalanine (YF1, YF3) have lost some or all of the capacity to mediate the activation of S6 kinase in response to insulin. None of the four mutants that contain deletions (spBam, spBamYF3, iBgl, T-t) elicit an insulin-dependent stimulation of S6 kinase. A previous study of the IRros hybrid receptor demonstrated that it was unable to cause either insulin-stimulated thymidine incorporation or glucose uptake (Ellis, L., Morgan, D. O., Jong, S.-M., Wang, L.-H., Roth, R. A., and Rutter, W. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5101-5105). In contrast, the IRros chimera appears to mediate the activation of S6 protein kinase by insulin. In further evaluating the biological activities of the IRros hybrid, we have examined its effects on a microtubule-associated protein-2 (MAP2) kinase that is thought to be an early target in the cascade of reactions leading to increased S6 phosphorylation (Sturgill, T. W., Ray, L. B., Erickson, E., and Maller, J. L. (1988) Nature 334, 715-718). We find that the IRros receptor stimulates the MAP2 protein kinase from 3- to 6-fold in insulin-treated cells, conferring more than a 30-fold increase in the insulin sensitivity of MAP2 kinase activation.

UR - http://www.scopus.com/inward/record.url?scp=0025268576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025268576&partnerID=8YFLogxK

M3 - Article

C2 - 2154457

AN - SCOPUS:0025268576

VL - 265

SP - 2713

EP - 2719

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -