Research Abstract:
My research program explores molecular structures and regulatory mechanisms of multi-purpose receptor systems known for such functions as pain and thermal perception, awakening and allergic responses. How do cells generate diverse forms of receptors for the mediators bradykinin (BK) and histamine (HIS) and link them to signaling pathways? How do signaling pathways in turn act upon the receptor systems? We explore how these receptor systems direct cellular growth and differentiated functions such as the production of neurites on neurons. The receptors modulate arousal, pain and irritant perception, blood flow and vascular permeability, and host defenses. They also regulate mitogenesis and protein synthesis, and link to the availability of growth regulators at both cell surface uptake transporters and intracellular phosphorylation pathways that transduce cell cycle regulation.
We study ligand-receptor recognition and activation of signal transduction, cellular trafficking pathways and membrane component flow in receptor regulation, and specific metabolic enzymes. Our major interest is how these receptor systems can be turned off or on. They particularly tend to become turned on too much, thus causing tissue damage. BK receptors mediate functions as diverse as cough reflexes and tissue remodeling; their tendency toward hyperactivity is fostered by signaling mechanisms that evoke multiple receptor forms. The HIS receptor system interacts with other membrane components and activities; for example, Na+- and Cl- - dependent transport of both HIS metabolites and polyamines into the cell regulates both receptor and growth regulatory activities. Our studies seek to understand receptor events at the level of individual cells and of cell-cell interaction, and how receptor hyperactivity may play a key role in development of conditions such as Alzheimer’s disease.
Selected Publications:
Jong YJI, Ford SR, Seehra K, Malave VB, Baenziger NL. Alzheimer’s disease skin fibroblasts selectively express a bradykinin signaling pathway mediating tau protein Ser phosphorylation. FASEB J 2003 17(15):2319-2321.
Jong YJI, Dalemar LR, Seehra K, Baenziger NL. Bradykinin receptor modulation in cellular models of aging and Alzheimer’s disease. Int Immunopharmacol 2002 2:1833-1840.
Dalemar L, Jong YJI, Wilhelm B, Baenziger NL. Protein kinases A and C rapidly modulate expression of human fibroblast B2 bradykinin receptor affinity forms. Eur J Cell Biol 1996 69:236-244.
Baenziger NL, Mack P, Jong YJI, et al. An environmentally regulated receptor for diamine oxidase modulates human endothelial cell/fibroblast histamine degradative uptake. J Biol Chem 1994 269:14892-14898.
Jong YJI, Dalemar LR, Wilhelm B, Baenziger NL. Human bradykinin-B2 receptors isolated by receptor-specific monoclonal antibodies are tyrosine phosphorylated. Proc Nat Acad Sci USA 1993 90:10994-10998.
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