Biff Forbush, PhD
Research & Publications
Biography
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Research Summary
Regulation of intracellular ion concentrations is essential to all living cells. The transport of ions mediated by specific membrane proteins underlies control of cell volume, epithelial transport, and the maintenance of transmembrane ion gradients which underlie electrical activity in nerve and muscle cells. Our work is directed towards understanding the mechanisms by which ion transport take place, and our attention is focused on a particular family of transport proteins, the cation-chloride cotransporters. Among these, the Na-K-Cl cotransporter uses the Na gradient to drive accumulation of cellular K and Cl and is a central element in the process of net salt transport in both secretory and absorptive epithelia. We are addressing questions of protein structure, of structure-function relationships, and of protein kinase-mediated regulation, in animal models and by expression of transport proteins in cell culture.
Speciailized Terms: Membrane Proteins; Epithelial Transport; Ion Transport; Na-K-Cl Cotransporter; Nerve Cells; Muscle Cells
Extensive Research Description
Coauthors
Research Interests
Membrane Proteins; Physiology; Sodium-Potassium-Chloride Symporters; Muscle Cells
Selected Publications
- Regulatory activation is accompanied by movements in the Cterminus of the Na‐K‐Cl cotransporter (NKCC1)Monette M, Forbush B. Regulatory activation is accompanied by movements in the Cterminus of the Na‐K‐Cl cotransporter (NKCC1). The FASEB Journal 2012, 26: 604.3-604.3. DOI: 10.1096/fasebj.26.1_supplement.604.3.
- Functional Analysis of Transmembrane Domain 3 in NKCC1Somasekharan S, Forbush B. Functional Analysis of Transmembrane Domain 3 in NKCC1. Biophysical Journal 2011, 100: 245a-246a. DOI: 10.1016/j.bpj.2010.12.1558.
- Sites of Regulated Phosphorylation that Control K-Cl Cotransporter ActivityRinehart J, Maksimova Y, Tanis J, Stone K, Hodson C, Zhang J, Risinger M, Pan W, Wu D, Colangelo C, Forbush B, Joiner C, Gulcicek E, Gallagher P, Lifton R. Sites of Regulated Phosphorylation that Control K-Cl Cotransporter Activity. Journal Of End-to-End-testing 2009, 138: 525-536. DOI: 10.1016/s9999-9994(09)20441-7.
- Apical membrane expression of NKCC2 is directed by a domain within its cytoplasmic C‐terminusCarmosino M, Gimenez I, Caplan M, Forbush B. Apical membrane expression of NKCC2 is directed by a domain within its cytoplasmic C‐terminus. The FASEB Journal 2008, 22: 935.4-935.4. DOI: 10.1096/fasebj.22.1_supplement.935.4.
- The Residues Determining Differences in Ion Affinities among the Alternative Splice Variants F, A, and B of the Mammalian Renal Na-K-Cl Cotransporter (NKCC2)*Giménez I, Forbush B. The Residues Determining Differences in Ion Affinities among the Alternative Splice Variants F, A, and B of the Mammalian Renal Na-K-Cl Cotransporter (NKCC2)*. Journal Of Biological Chemistry 2006, 282: 6540-6547. PMID: 17186942, DOI: 10.1074/jbc.m610780200.
- PASK (Proline-Alanine-rich STE20-related Kinase), a Regulatory Kinase of the Na-K-Cl Cotransporter (NKCC1)*Dowd BF, Forbush B. PASK (Proline-Alanine-rich STE20-related Kinase), a Regulatory Kinase of the Na-K-Cl Cotransporter (NKCC1)*. Journal Of Biological Chemistry 2003, 278: 27347-27353. PMID: 12740379, DOI: 10.1074/jbc.m301899200.
- Ion transport and ligand binding by the Na–K–Cl cotransporter, structure–function studiesIsenring P, Forbush B. Ion transport and ligand binding by the Na–K–Cl cotransporter, structure–function studies. Comparative Biochemistry And Physiology Part A Molecular & Integrative Physiology 2001, 130: 487-497. PMID: 11913460, DOI: 10.1016/s1095-6433(01)00420-2.
- Modulation of Ion Transport by Direct Targeting of Protein Phosphatase Type 1 to the Na-K-Cl Cotransporter*Darman R, Flemmer A, Forbush B. Modulation of Ion Transport by Direct Targeting of Protein Phosphatase Type 1 to the Na-K-Cl Cotransporter*. Journal Of Biological Chemistry 2001, 276: 34359-34362. PMID: 11466303, DOI: 10.1074/jbc.c100368200.