Two closely related receptor‐type tyrosine phosphatases are differentially expressed during rat lung development

Abstract

Transmembrane protein tyrosine phosphatases (PTPases) comprise a newly identified class of receptor-like molecules. In most cases their ligands and the substrates they dephosphorylate are not known. In order to begin to explore the functions of the PTPases in cell physiology and in mammalian development, we examined the expression patterns of two closely related receptor-type tyrosine phosphatase genes, namely LAR and PTPG, in fetal rat lung and in selected adult rat tissues. In the lung, in situ hybridization and immunohistochemistry show that the LAR mRNA and protein are expressed exclusively in the epithelium. In the early embryonic or fetal lung (day 13 to 18) LAR is expressed by all of the epithelial cells of the forming bronchial tree. This widespread pattern of expression is lost later in fetal Life (day 21) as the lung matures and acquires the morphologic and biochemical features of the adult organ. LAR gene expression is then confined to two epithelial progenitor cells of the distal airways, namely the bronchiolar Clara cell and the alveolar type I1 cell. The LAR gene products were also found abundantly expressed in epithelial progenitor cells of adult esophagus, skin, and small intestine, all of which are continuously renewing epithelia. The rat PTPG gene, on the other hand, is specifically expressed in the mesenchyme of the developing lung. The level of the PTPG mRNA decreases as the lung matures. These results suggest that the two closely related receptor-type tyrosine phosphatases are differentially expressed in a tissue-specific fashion. They are expressed mostly in proliferating cells or in cells which have potential to proliferate. Therefore, one function of the two receptor-like tyrosine phosphatases may be to regulate proliferation and/or differentiation of different types of cells during development, during normal cell turnover, and during adult tissue repair.

Epithelial marker genes are expressed in cultured embryonic rat lung and in vivo with similar spatial and temporal patterns.

“…and T l a (Type I cells) (Rishi et al, 1995). Localization of LAR mRNA (Type I1 and Clara cells) in normal fetal lung has been reported elsewhere (Katsura et al, 1995); we present here new observations on cultured lung. The following cDNA fragments for these genes were cloned into the pBluescript SK+ vector, and appropriate linearized templates were prepared for generating 3'S-labeled.…”

“…Amplified DNA was analyzed by agarose gel electrophoresis. Oligonucleotide primers for &actin, SP-A, Tla, are listed elsewhere (Rishi et al, 1995); for SP-B and SP-C (Cardoso et al, 1995), and for LAR (Katsura et al, 1995). Primers for CClO amplification were (5') CACTGT-GCTCATGCTGTCC and (3') GCTCACACAGAGGACTTGTTAGG.…”

“…We selected genes for study that have wellcharacterized sites of expression in the distal adult lung. These include surfactant proteins (SP) SP-A, SP-B, CC10, a receptor-type tyrosine phosphatase LAR (Katsura et al, 1995), all of which are expressed in rodents in both alveolar Type I1 and bronchiolar Clara cells, SP-C, a marker for Type I1 cells, and Tla, a marker for Type I cells (Williams et al, 1996;Rishi et al, 1995;Williams and Dobbs, 1990;Dobbs et al, 1988). Using a monoclonal antibody, we also characterized Tla protein expression in vitro by immunohistochemistry to compare it with in vivo expression (Williams et al, 1996;Williams and Dobbs, 1990).…”

The Second Catalytic Domain of Protein Tyrosine Phosphatase δ (PTPδ) Binds to and Inhibits the First Catalytic Domain of PTPς

“…This suggests that LAR or its other family members may have a parallel role in vertebrates as well. Indeed, PTP, PTP␦, and LAR were previously shown to be strongly expressed during development in selected regions within the central nervous system and the peripheral nervous system, as well as in other epithelial and neuroepithelial cells (17,18,23,34,35,45,46,49), and a recent gene knockout of LAR has demonstrated a reduction in the size of cholinergic neurons and defects in hippocampal cholinergic innervation (51).…”

Specific inhibition of FGF-induced MAPK activation by the receptor-like protein tyrosine phosphatase LAR

“…LAR is thought to participate in tyrosine phosphorylation-dependent signal transduction and in the regulation of cell growth. Thus, expression of LAR correlates with cell proliferation (Katsura et al, 1995). Furthermore, overexpression of LAR in cultured cells reduces both the extent of phosphorylation and the stability of p130 CAS , an important signaling protein, as well as induces apoptosis (Weng et al, 1998(Weng et al, , 1999.…”