Two novel cDNAs, IA-1 and IA-2, isolated from a human insulinoma subtraction library (ISL-153) were subjected to intensive studies. IA-1 gene was isolated and characterized to be an intronless gene which localized at chromosome 20p11.2 by fluorescence in situ hybridization. We have conducted a study of IA-1 gene expression in a panel of 64 endocrine and non-endocrine human lung cancer cell lines and compared it with two other neuroendocrine markers, chromogranin A and L-dopa decarboxylase. The result indicated that IA-1 is a candidate marker of neuroendocrine differentiation of human lung tumors. IA-1 mRNA was detected by Northern blot analysis in 97% (30/31) of small cell lung cancer (SCLC) cell lines. In contrast, IA-1 mRNA was detected in only 13% (4/30) of non-small cell lung cancer (NSCLC) cell lines. In most of the lung cancer cell lines examined, IA-1 showed high concordance with the other neuroendocrine markers, L-dopa decarboxylase and chromogranin A. The second cDNA, IA-2, was characterized to be a new member of receptor-type protein tyrosine phosphatase which expressed in normal enriched islets and brain tissues. We have also cloned and sequenced the mouse counterpart of IA-2 from a normal mouse brain library. Mouse brain IA-2 revealed 85% and 92% homology to the human insulinoma IA-2 molecule in nucleotide sequence and amino acid sequence respectively. Furthermore, both molecules share 99.7% identify in a stretch of 300 amino acids of intracellular PTP domain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000423-09
Application #
3753537
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1994
Total Cost
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Cai, Tao; Hirai, Hiroki; Fukushige, Tetsunari et al. (2009) Loss of the transcriptional repressor PAG-3/Gfi-1 results in enhanced neurosecretion that is dependent on the dense-core vesicle membrane protein IDA-1/IA-2. PLoS Genet 5:e1000447
Kim, Soo Mi; Theilig, Franziska; Qin, Yan et al. (2009) Dense-core vesicle proteins IA-2 and IA-2{beta} affect renin synthesis and secretion through the {beta}-adrenergic pathway. Am J Physiol Renal Physiol 296:F382-9
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Li, Na; Shigihara, Toshikatsu; Tzioufas, Athanasios G et al. (2007) Human chorionic gonadotropin prevents Sjogren's syndrome-like exocrinopathy in mice. Arthritis Rheum 56:2211-5
Kubosaki, Atsutaka; Nakamura, Shinichiro; Clark, Anne et al. (2006) Disruption of the transmembrane dense core vesicle proteins IA-2 and IA-2beta causes female infertility. Endocrinology 147:811-5
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