CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Boney, C. M.
Right arrow Articles by Frackelton, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Boney, C. M.
Right arrow Articles by Frackelton, A. R., Jr.
Cell Growth & Differentiation Vol. 12, 379-386, July 2001
© 2001 American Association for Cancer Research

Src Family Tyrosine Kinases Participate in Insulin-like Growth Factor I Mitogenic Signaling in 3T3-L1 Cells1

Charlotte M. Boney2, Hiroko Sekimoto, Philip A. Gruppuso and A. Raymond Frackelton, Jr.

Department of Pediatrics, Brown University and Rhode Island Hospital, Providence, Rhode Island 02903 [C. M. B., H. S., P. A. G.]; Department of Medicine, Roger Williams Hospital, Providence, Rhode Island 02908 [A. R. F.]; and Department of Pathology and Laboratory Medicine, Brown University [A. R. F.], Providence, Rhode Island 02903

Insulin-like growth factor-I (IGF-I) stimulates proliferation and differentiation of many cell types, including preadipocytes. We have previously shown that IGF-I stimulates proliferation of 3T3-L1 preadipocytes through activation of the extracellular regulated kinase (ERK)-1 and -2 mitogen-activated protein kinase (MAPK) pathway, and that IGF-I-stimulated MAPK is predominantly downstream of Shc, not IRS-1 phosphorylation. The Src family of nonreceptor tyrosine kinases has been shown to mediate the mitogenic effects of other growth factors that also activate Shc and the ERK-1 and -2 MAPKs. Although Src family kinases (SFK) have been implicated in IGF-I action, no specific role for SFKs in IGF-I regulation of mitogenesis has been previously demonstrated. We studied the role of SFKs in IGF-I mitogenic signaling in 3T3-L1 preadipocytes. The SFK-selective inhibitor PP1 completely inhibited both IGF-I-stimulated DNA synthesis and MAPK activation in proliferating 3T3-L1 cells. PP1 inhibited IGF-I phosphorylation of Shc but not of IRS-1. In addition, IGF-I activation of MAPK was inhibited in proliferating cells transiently transfected with a dominant-negative c-Src. Finally, the kinetics of SFK and MAPK activation by IGF-I suggest that SFKs may act upstream of MAPK. IGF-I activation of SFK members c-Src and Fyn occurred within 1 min of treatment, and activity was back to baseline by 10 min. Our previous studies found that IGF-I activation of MAPK peaked at 5 min and was also back to baseline by 10 min. Our results are the first to demonstrate that SFKs mediate IGF-I mitogenic signaling in 3T3-L1 cells and add to the growing body of evidence that SFKs play a crucial role in IGF-I action.




This article has been cited by other articles:


Home page
Proc. Natl. Acad. Sci. USAHome page
G. Oligny-Longpre, M. Corbani, J. Zhou, M. Hogue, G. Guillon, and M. Bouvier
Engagement of {beta}-arrestin by transactivated insulin-like growth factor receptor is needed for V2 vasopressin receptor-stimulated ERK1/2 activation
PNAS, April 24, 2012; 109(17): E1028 - E1037.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
G. Xi, X. Shen, L. A. Maile, C. Wai, K. Gollahon, and D. R. Clemmons
Hyperglycemia Enhances IGF-I-Stimulated Src Activation via Increasing Nox4-Derived Reactive Oxygen Species in a PKC{zeta}-Dependent Manner in Vascular Smooth Muscle Cells
Diabetes, January 1, 2012; 61(1): 104 - 113.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
G. Xi, X. Shen, and D. R. Clemmons
p66shc Inhibits Insulin-like Growth Factor-I Signaling via Direct Binding to Src through Its Polyproline and Src Homology 2 Domains, Resulting in Impairment of Src Kinase Activation
J. Biol. Chem., March 5, 2010; 285(10): 6937 - 6951.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
J. Lieskovska, Y. Ling, J. Badley-Clarke, and D. R. Clemmons
The Role of Src Kinase in Insulin-like Growth Factor-dependent Mitogenic Signaling in Vascular Smooth Muscle Cells
J. Biol. Chem., September 1, 2006; 281(35): 25041 - 25053.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
B. M. Thobe, M. Frink, M. A. Choudhry, M. G. Schwacha, K. I. Bland, and I. H. Chaudry
Src family kinases regulate p38 MAPK-mediated IL-6 production in Kupffer cells following hypoxia
Am J Physiol Cell Physiol, September 1, 2006; 291(3): C476 - C482.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
S. Hardy, G. G. St-Onge, E. Joly, Y. Langelier, and M. Prentki
Oleate Promotes the Proliferation of Breast Cancer Cells via the G Protein-coupled Receptor GPR40
J. Biol. Chem., April 8, 2005; 280(14): 13285 - 13291.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Endocrinol. Metab.Home page
Y.-H. Chen, P.-F. Hung, and Y.-H. Kao
IGF-I downregulates resistin gene expression and protein secretion
Am J Physiol Endocrinol Metab, April 8, 2005; 288(5): E1019 - E1027.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Q.-L. Cui, W.-H. Zheng, R. Quirion, and G. Almazan
Inhibition of Src-like Kinases Reveals Akt-dependent and -independent Pathways in Insulin-like Growth Factor I-mediated Oligodendrocyte Progenitor Survival
J. Biol. Chem., March 11, 2005; 280(10): 8918 - 8928.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Z. He, Y.-Y. Cho, W.-Y. Ma, H. S. Choi, A. M. Bode, and Z. Dong
Regulation of Ultraviolet B-induced Phosphorylation of Histone H3 at Serine 10 by Fyn Kinase
J. Biol. Chem., January 28, 2005; 280(4): 2446 - 2454.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. J. Hupfeld, J. L. Resnik, S. Ugi, and J. M. Olefsky
Insulin-induced {beta}-Arrestin1 Ser-412 Phosphorylation Is a Mechanism for Desensitization of ERK Activation by G{alpha}i-coupled Receptors
J. Biol. Chem., January 14, 2005; 280(2): 1016 - 1023.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
G. Blum, A. Gazit, and A. Levitzki
Development of New Insulin-like Growth Factor-1 Receptor Kinase Inhibitors Using Catechol Mimics
J. Biol. Chem., October 17, 2003; 278(42): 40442 - 40454.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
A. Myoui, R. Nishimura, P. J. Williams, T. Hiraga, D. Tamura, T. Michigami, G. R. Mundy, and T. Yoneda
C-Src Tyrosine Kinase Activity Is Associated with Tumor Colonization in Bone and Lung in an Animal Model of Human Breast Cancer Metastasis
Cancer Res., August 15, 2003; 63(16): 5028 - 5033.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
Y. Huang, S.-O. Kim, J. Jiang, and S. J. Frank
Growth Hormone-induced Phosphorylation of Epidermal Growth Factor (EGF) Receptor in 3T3-F442A Cells: MODULATION OF EGF-INDUCED TRAFFICKING AND SIGNALING
J. Biol. Chem., May 23, 2003; 278(21): 18902 - 18913.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
P. A. Kiely, A. Sant, and R. O'Connor
RACK1 Is an Insulin-like Growth Factor 1 (IGF-1) Receptor-interacting Protein That Can Regulate IGF-1-mediated Akt Activation and Protection from Cell Death
J. Biol. Chem., June 21, 2002; 277(25): 22581 - 22589.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2001 by the American Association of Cancer Research.