Gillian Air  /  Sanjay Bidichandani  /  Robert Broyles
  Paul DeAngelis  /  Jay Hanas  /  Martin Levine  /  Guangpu Li 

Jialing Lin  /  Hiroyuki Matsumoto  / Blaine Mooers /  Ann Louise Olson 

Karla Rodgers  /  Robert Steinberg  /  Leon Unger  /  Paul Weigel   /  Christopher West 

Somatic-cell and molecular genetic analysis of transmembrane signaling systems in cultured mammalian cell lines; structure, function, and regulation of cyclic AMP- dependent protein kinase.

Selective protein phosphorylation underlies regulation of cellular metabolism by a wide variety of agents, ranging from hormones and growth factors to tumor promoters and oncogenes. Of the many effector-regulated phosphorylation systems in mammalian cells, the system activated by cyclic AMP (cAMP) has been studied most intensively and has served as a prototype for understanding the role of protein phosphorylation in cellular control. Our research uses cultured S49 mouse lymphoma cells and products from recombinant bacterial systems for genetic, physiological, and biochemical analyses of the cAMP response pathway with a major focus on the intracellular transducer for the pathway-cAMP-dependent protein kinase. Using mutations affecting kinase regulatory subunit identified in non-responsive lymphoma cell mutants and transferred to bacterial expression plasmids, we have been studying in molecular detail the binding and allosteric interactions by which cAMP promotes activation of the cAMP-dependent protein kinase. Motivated initially by isolation of a mutant cell almost completely deficient in cAMP-dependent protein kinase, we have also been studying the synthesis, maturation, and turnover of the catalytic subunit of the enzyme. We showed recently that efficient catalytic subunit activity requires phosphorylation of an endogenous threonine residue, and we are currently working on characterization and purification of an enzyme that appears to be responsible for this phosphorylation in mammalian cells. One of the observed regulatory subunit lesions results from a transition mutation at a site of DNA methylation; the high spontaneous rate of occurrence of this lesion has led us to investigate the role of DNA methylation in spontaneous mutagenesis. Since about 25-30% of all point mutations underlying human disease appear to involve transitions at potential methylation sites, these studies have immediate relevance to molecular medicine.

Recent Publications:
Goentzel BJ, Weigel PH, Steinberg RA 2006: Recombinant human hyaluronan synthase 3 is phosphorylated in mammalian cells.  Biochem J 396:347-354.

Lamb D, Steinberg RA 2002: Anti-proliferative effects of 8-chloro-cAMP and other cAMP analogs are unrelated to their effects on protein kinase A regulatory subunit expression. J Cell Physiol 192:216-224.

Gan J, Zhang YL, Carter KB, Cauthron RD, Steinberg RA  1999: On the spontaneous mutability of CpG sites in cultured S49 mouse lymphoma cells.  Somat Cell Mol Genet. 25:129-45.

Cauthron, RD, Carter, KB, Liauw, S, and Steinberg, RA 1998: Physiological phosphorylation of protein kinase A at Thr-197 is by a protein kinase A kinase. Mol. Cell Biol. 18:1416-1423. 

Home     Graduate Programs     Departmental Information     Faculty
Departmental Directory     Seminars     Major Facilities     Employment Opportunities     Intranet