Gene Sequencing and Tissue Expression of Unknown Isoforms of an Angiotensin II Type 2 Receptor Interacting Protein, ATIP, in the Rat

Abstract

To investigate the expression of the unknown angiotensin II type 2 receptor interacting protein (ATIP) isoforms in the rat we used the known sequences of human and mouse ATIP to design sequencing primers to enable us to sequence rat ATIP3 and ATIP4. Exon 4, which is present in human but not mouse ATIP, was not identified in the coding region of rat ATIP. The expression levels of these genes in a range of rat tissues were examined, and we concluded that there is little similarity in the relative tissue distribution of the various ATIP isoforms in rat and human.

Function and expression of ATIP and its variants in cardiomyoblast cell line H9c2

“…These findings are in contrast to the relative expression of the ATIP variants in rat left ventricle, where ATIP1 mRNA was the predominantly expressed ATIP variant followed by ATIP3 mRNA. 39 ATIP protein was identified in both whole myoblasts and myotubules using immunohistochemical techniques (Figure 2(a) and (b)); cytoplasmic staining for tATIP in whole cells was significantly higher in myoblasts than myotubules (Figure 1(i)). Unfortunately, due to the non-specific nature of the anti-tATIP antibody used in the immunohistochemical studies, it was not possible to determine the relative expression of the individual ATIP proteins in whole cells.…”

“…36,37 Five ATIP isoforms designated ATIP1, ATIP2, ATIP3a, ATIP3b and ATIP4, 38 have been identified in humans, whereas only ATIP1, ATIP3, which corresponds to human ATIP3b, and ATIP4 have been identified in the rat. 39 In a range of normal and cancer cell lines, it has been demonstrated that ATIP1, working in concert with the AT2-receptor, inhibits growth factor-induced and Ang II-induced cell proliferation via inhibition of mitogen-activated protein kinase (MAPK). 37,38,40,41 Beyond this, little definite is known regarding the intracellular-signalling pathways via which the ATIP isoforms act; for instance, initial reports indicated that ATIP1 did not act as a phosphatase nor did it interact directly with protein tyrosine phosphatase 1 (SHP-1), 36,37 a soluble protein tyrosine phosphatase that inhibits growth factor receptor signalling and is activated following stimulation of the AT2-receptor.…”

“…36,37 Five ATIP isoforms designated ATIP1, ATIP2, ATIP3a, ATIP3b and ATIP4, 38 have been identified in humans, whereas only ATIP1, ATIP3, which corresponds to human ATIP3b, and ATIP4 have been identified in the rat. 39 In a range of normal and cancer cell lines, it has been demonstrated that ATIP1, working in concert with the AT2-receptor, inhibits growth factor-induced and Ang II-induced cell proliferation via inhibition of mitogen-activated protein kinase (MAPK). 37,38,40,41…”

Microtubule-Associated Protein ATIP3, an Emerging Target for Personalized Medicine in Breast Cancer

“…To date, no functional difference has been reported between the two polypeptides. In rodents, the ortholog MTUS1 gene comprises 15 coding exons that are also alternatively spliced [ 13 , 16 ] to generate 3 different ATIP isoforms (designated ATBP50, ATBP135, and ATBP60 in the mouse) with high sequence homology to human ATIP1, ATIP3 and ATIP4, respectively. The Xenopus MTUS1 gene ortholog encodes the ICIS protein, which exhibits structural homology with the mammalian ATIP3 isoform [ 14 ].…”

Novel players in cardioprotection: Insulin like growth factor-1, angiotensin-(1–7) and angiotensin-(1–9)

“…Five ATIP isoforms (ATIP1, 2, 3a, 3b and 4) have been identified [156]. Orthologues of rat ATIP3b and 4 have been detected in humans [157]. In a broad range of normal and cancer cell lines, ATIP1 working with AT2R inhibits growth factor-induced and Ang II-induced cell proliferation via MAPK inhibition [155,156,158,159] (Figure 2).…”