Lawrence Stanton Argetsinger, PHD

Research Assistant Professor
Univ of Michigan Medical School
Dept of Molecular & Integrative Physiology

Biographical Sketch:
Growth hormone is critical for the regulation of both longitudinal growth and numerous metabolic processes, including fat metabolism. In 1993, my work in the Carter-Su lab determined that JAK2 was an essential component of growth hormone (GH) signaling. I have continued to elucidate the molecular mechanisms by which GH regulates function at the cellular level. In an effort to identify binding partners for JAK2, I have mapped phosphorylation sites in JAK2 using both 2-D peptide mapping and mass spectrometry. I have determined that complexes associated with insulin receptor substrate 1 and 2 are recruited and activated in response to GH. In work with postdoctoral students, Silac-based mass spectrometry was used to identify proteins phosphorylated in response to GH. Because JAK2 is activated in response to numerous cytokines, these studies have the potential to reveal signaling pathways utilized by a broad range of ligands. One of the binding partners for JAK2 discovered (using the yeast-2-hybrid assay) by Liangyou Rui when he was a graduate student in the laboratory was the adaptor protein SH2B1. In work with graduate students, the phosphorylated tyrosine in JAK2 that interacts with SH2B1 was determined. In addition, the sites of phosphorylation in SH2B1 were identified. These sites of phosphorylation in SH2B1 were recently determined to be essential for maximal GH-dependent cell migration. Genetic studies have recently identified SH2B1 as a potential human obesity gene. I have worked with both graduate students and postdoctoral fellows and our collaborators, Sadaf Farooqi (Cambridge, UK) and Joshua Coon (Univ. Wisconsin), to start to elucidate how disruptions in SH2B1 signaling lead to morbid obesity and in some patients, aggressive behavior. Knowledge that should give additional needed insight into regulation of fat metabolism and maladaptive behavior in the general population.
Papers:
S04 GH at the Cutting Edge
S04-2 SH2B1: A Critical Scaffold Protein for GH-Mediated Cell Motility