Dr. Carter-Su received her Bachelor of Science in Applied Mathematics and Biomedical Sciences from Brown University. She received her MS and PhD in Biophysics from the University of Rochester where she worked with Dr. George Kimmich analyzing the energetics of intestinal transport of glucose and amino acids. Following postdoctoral studies at Brown University with Dr. Michael Czech looking at the molecular basis for insulin regulation of glucose transport in fat cells, she joined the faculty in Physiology at the University of Michigan Medical School. In addition to her primary appointment in the Department of Molecular and Integrative Physiology, she holds a joint appointment in the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine. She also serves as the Associate Director of the NIH funded Michigan Diabetes Research Center.
Areas of Interest
A major and longstanding interest of our laboratory is the delineation of the cellular and molecular mechanisms by which growth hormone (GH) regulates body growth and metabolism. GH is the primary hormone responsible for longitudinal body growth; it also regulates metabolism and other body functions. The GH receptor is a member of the cytokine family of cell surface receptors. Our laboratory was one of the first to show that cytokines activate JAK family kinases and helped delineate the JAK-Stat pathway for cytokine receptors, the primary signaling pathway for more than 25 different ligands. We showed that binding of GH to its receptor rapidly activates the GH receptor-associated tyrosine kinase JAK2 and the Stat transcription factors. We have used a variety of approaches to identify multiple additional signaling proteins and pathways that are initiated by GH as a consequence of its activation of JAK2. We also study how JAK2 is activated in response to ligand binding and subsequently deactivated. Because JAKs are key signaling proteins for multiple cytokines important for multiple body functions, our studies are relevant to many diseases and syndromes, including short stature, metabolic syndrome, obesity, myeloproliferative disorders, multiple cancers and diseases involving the immune system (e.g. rheumatoid arthritis, severe combined immunodeficiency disease [SCID]).
One JAK2 binding protein identified by our lab is the scaffolding protein SH2B1. SH2B1 is recruited to activated JAK2 in response to GH and the satiety hormone leptin. SH2B1 is also recruited to a variety of activated receptor tyrosine kinases, including the receptors for multiple neurotrophins, insulin, and insulin-like growth factor. Mice lacking SH2B1 are obese and insulin-resistant. We have recently initiated a collaboration with Dr. Farooqi’s group at the University of Cambridge, England. The Farooqi lab has identified patients with point mutations in SH2B1. These patients exhibit severe childhood obesity, insulin resistance, and sometimes maladaptive behavior and short stature. We are currently investigating at the cellular and molecular levels how SH2B1 affects such a diverse array of important body functions. We have implicated SH2B1 in cell motility and nerve growth factor-dependent neuronal differentiation, and shown that SH2B1 cycles between the plasma membrane and the nucleus. We have shown that the human mutations disrupt at least some of these functions of SH2B1. We have also determined that phosphorylation of specific residues in SH2B1 dramatically alters the subcellular localization and function of SH2B1, and that the different isoforms of SH2B1 exhibit differences in function. Our laboratory uses standard immunological, biochemical, recombinant DNA, and imaging techniques, phosphopeptide mapping, phosphoproteomics, microarrays, confocal microscopy, total internal reflection fluorescence microscopy (TIRFM), and fluorescence recovery after photobleaching (FRAP). Animal studies looking at the function of SH2B1 isoforms in the brain are also being initiated.
Argetsinger, L. S.#, G. S. Campbell#, X. Yang, B. A. Witthuhn, O. Silvennoinen, J. N. Ihle and C. Carter-Su. Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell 74:237-244 (1993) (#Authors contributed equally)
Yu, C.-L., D. J. Meyer, G. S. Campbell, A. C. Larner, C. Carter-Su, J. Schwartz and R. Jove. Enhanced DNA-Binding Activity of a Stat3-Related Protein in Cells Transformed by the Src Oncoprotein. Science 269:81-83 (1995) (543 citations)
Maures, T. J., L. Chen, C. Carter-Su. Nucleocytoplasmic shuttling of the adapter protein SH2B1b (SH2-Bb) is required for nerve growth factor (NGF)-dependent neurite outgrowth and enhancement of expression of a subset of NGF-responsive genes. Mol. Endocrinol. 23:1077-1091 (2009).
Argetsinger, L. A., J. A. Stuckey, S. A. Robertson, R. I. Koleva, J. M. Cline, J. A. Marto, M. G. Myers, Jr., and C. Carter-Su. Tyrosines 868, 966, and 972 in the kinase domain of JAK2 are autophosphorylated and required for maximal JAK2 kinase activity. Mol. Endocrinol. 24:1062-1076 (2010).
Maures, T. J., H-W. Su, L. S. Argetsinger, S. Grinstein, and C. Carter-Su. Phosphorylation controls a dual function polybasic NLS in the adapter protein SH2B1b to regulate its cellular function and distribution. J. Cell Sci. 124:1542-1552 (2011).
Ray, B.#, H. K. Kweon#, L. S. Argetsinger, D. C. Fingar, P. C. Andrews and C. Carter-Su. Identification of novel growth hormone-regulated phosphorylation sites by quantitative phosphoproteomics. Mol. Endo. 26:1056-1073 (2012) (# authors contributed equally).
Doche, M.E.#, E. G. Bochukova#, H.-W Su, L. Pearce, J. M. Keogh, E. Henning, J. M. Cline, A. Dale, T. Cheetham, I. Barroso, L. S. Argetsinger, S. O-Rahilly, L. Rui, C. Carter-Su, I. S. Farooqi. SH2B1 mutations are associated with maladaptive behavior and obesity in humans. J. Clin. Invest. 122:4732-4736 (2012) (#, + authors contributed equally).
Su, H-W, N. J. Lanning, D. L. Morris, L. S. Argetsinger, C. N. Lumeng, and C. Carter-Su. Phosphorylation of the adaptor protein SH2B1β regulates its ability to enhance growth hormone (GH)-dependent macrophage motility. J. Cell Sci. 126:1733-1743 (2013).
Honors & Awards
- Sc.B. Magna cum laude with honors in Applied Mathematics, 1972
- Charles H. Best Award for Outstanding Fellow of the Juvenile Diabetes Foundation, 1978
- Eli Lilly Lecturer for the Lawson Wilkins Pediatric Endocrine Society, 1994
- University of Michigan Faculty Recognition Award, 1995
- Sarah Goddard Power Award, University of Michigan, 1999
- Roy O. Greep Lecture Award for outstanding contributions to research in endocrinology, The Endocrine Society, 2000
- Distinguished Lecturer in Medical Sciences for 2001, Department of Medicine, Mayo Clinic, 2001
- NIH grant DK34171 awarded MERIT status, 2001
- Distinguished Faculty Lectureship Award in BioMedical Research, University of Michigan Medical School, 2002
- Bodil Schmidt-Nielsen Distinguished Mentor and Scientist Award from the American Physiological Society, 2004
- Molecular Endocrinology’s Outstanding Reviewer for 2007
- Goldberg Lecture in Signal Transduction and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, The University of Minnesota-Twin Cities, 2008
- Rackham Distinguished Faculty Achievement Award, University of Michigan, 2011
- Elected Fellow of American Association for the Advancement of Science (AAAS), 2011
- Henry Sewall Collegiate Professor of Physiology, University of Michigan, 2012
- Anita H. Payne Distinguished University Professor of Physiology, University of Michigan, 2013
- ScB, Brown University, Providence, Rhode Island; Sc.B. (Applied Mathematics-Biomedical Sciences), 1972
- Ph.D., University of Rochester School of Medicine & Dentistry, Rochester, N.Y.; (Biophysics; Advisor: Dr. George Kimmich), 1978
- Juvenile Diabetes Fdn Postdoctoral Fellow, Brown University, Providence, R.I. (Regulatory Biochemistry; Advisor: Dr. Michael Czech), 1978-1981