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Contact Information:
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester, New York 14642
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Medical Center, Room 4-8557
Phone: (585) 275-4933
Fax: (585) 273-2652 |
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Research Overview
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| The major goal of Dr. Hinkle's research is to understand how hormone binding to a plasma
membrane receptor triggers a characteristic sequence of cellular responses. Established lines of
anterior pituitary cells are used as model systems to investigate regulation of cell growth
and hormone secretion, particularly by the hypothalamic peptide TRH. Activation of the TRH receptor,
which is coupled to G proteins, stimulates phosphoinositide turnover and increases cytoplasmic calcium
and protein kinase C activity by well established pathways, but TRH stimulates other kinase
cascades by pathways that are currently unknown. Cultures of pancreatic islet cells are used
to study the molecular mechanisms involved in regulation of insulin secretion by glucose and
other agents. Calcium is a key regulator of exocytosis and transcription in both of these model
systems. In order to dissect the complex calcium response to hormones, several fluorescence imaging
techniques are used to monitor the free calcium concentration in the cytoplasm and endoplasmic reticulum
of individual cells. Many studies focus on how specificity in signaling is achieved. The intracellular
signals generated by hormonal activation are transient, and cells undergo rapid and selective
desensitization following exposure to hormone. Current work also attempts to understand the
mechanisms responsible for the desensitization process. Mutant receptors, dominant-negative mutants of
proteins involved in signaling and trafficking, and cells from knockout mice are used in these
investigations. The subcellular distribution of membrane receptors and other key signaling molecules
is monitored by several approaches, including microscopic localization of fluorescently-labeled hormones
and GFP-tagged proteins, in an attempt understand signal transduction, desensitization and resensitization
at a cellular level.
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Recent Publications
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Cook, L.B., and Hinkle, P.M. (2004) Agonist-dependent up-regulation of thyrotrophin-releasing hormone receptor protein. Biochem. J. 380:815-821.
Cook, L.B. and Hinkle, P.M. (2004) Fate of internalized TRH receptors monitored with a timer fusion protein. Endocrinology 145:3095-3100.
Jones, B.W. and Hinkle, P.M. (2005) Beta-arrestin mediates desensitization and internalization but does not affect dephosphorylation of the thyrotropin-releasing hormone receptor. J. Biol. Chem. 280:38346-38354.
Song, G.J. and Hinkle, P. M. (2005) Regulated dimerization of the thyrotropin-releasing hormone receptor affects receptor trafficking but not signaling. Mol. Endocrinol. 19:2859-2870.
PubMed Publication List
PubMed is maintained by the National
Library of Medicine
and provides complete abstracts of all 'hinkle pm' publications,
as well as links to the full text of many articles (at journal
homepages).
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