Disease relevance of PDZK1IP1

• The protein cluster formed by PDZK1, MAP17, and cMOAT is upregulated in a significant number of human carcinomas originating in the colon, breast, lung, and kidney [1].
• Immunhistologic staining of frozen sections derived from lesional skin of bullous pemphigoid und pemphigus vulgaris indicated that pKe#192/MAP17 was upregulated in the epidermis adjacent to the blister [2].
• Taken together, our data show an independent activation of MAP17 promoter that can be driven by oncogenes and that might explain the common overexpression of MAP17 in human carcinomas [3].

High impact information on PDZK1IP1

• Our results show striking coexpression of SCL and its immediate downstream neighbor, MAP17, suggesting that they share regulatory elements [4].
• Our data show conserved synteny between zebrafish and mammalian SCL and MAP17 loci, thus suggesting the likely genomic domain necessary for the conserved pattern of SCL expression [5].
• However, MAP17 is expressed abundantly in carcinomas arising from kidney, colon, lung, and breast, in some cases with a membrane-associated apical glandular distribution [6].
• In normal tissues, MAP17 is expressed in significant amounts only in the kidney, where it was localized to the brush border of proximal tubular epithelial cells [6].
• In tissue culture, MAP17 was localized to the cell membrane in areas of cell-cell contact, ie, the distribution of cell-function-associated proteins [6].

Biological context of PDZK1IP1

• Finally, cotransfection of MAP17 and NHERF3 prevented the adaptive upregulation of phosphate transport activity in OK cells in response to low extracellular phosphate [7].
• Transfection of MAP17 into the HT29 carcinoma cell line markedly decreased cell proliferation in vitro and tumor growth in vivo, suggesting that MAP17 plays a role, either direct or indirect, in the control of cell proliferation [8].
• In an attempt to elucidate the function of MAP17, we screened a human kidney cDNA library for interacting proteins using the yeast two-hybrid system and isolated a novel protein containing PDZ protein interaction domains, which we have named PDZK1 [8].
• PDZK1 may represent the link between the cell membrane-where it interacts with MAP17-and other cytoplasmic proteins involved in biologic functions such as cell proliferation, differentiation, and ion transport [8].

Anatomical context of PDZK1IP1

• The membrane-associated protein pKe#192/MAP17 in human keratinocytes [2].
• Rat kidney MAP17 induces cotransport of Na-mannose and Na-glucose in Xenopus laevis oocytes [9].
• MAP17 is responsible for mannose transport expression in oocytes by rat kidney cortex mRNA [9].
• Anti-SPAP antibodies visualized by secondary fluorescein isothiocyanate (FITC)-labelled antibodies were bound to the postacrosomal part of the spermatozoa, indicating that SPAP is specifically bound to this area, and directly interacts with the spermatozoa [10].

Associations of PDZK1IP1 with chemical compounds

• When the dopamine D1-like receptor was activated with fenoldopam, both NaPiIIa and MAP17 also accumulated in the TGN [7].
• Several PDZ domain-containing proteins interact with its COOH terminus while the small membrane protein MAP17 interacts with its NH(2) end [7].

Physical interactions of PDZK1IP1

• Results obtained by various in vitro analyses suggested that MAP17 interacts with the fourth domain of PDZK1 but not with other PDZ proteins localized in proximal tubular brush borders [11].

Other interactions of PDZK1IP1

• Unexpectedly, we found that hepatic overexpression of SPAP in mice resulted in liver deficiency of PDZK1 [12].
• The interactions of MAP17 with the NHERF proteins and with NaPiIIa were further analyzed in opossum kidney (OK) cells [7].

Analytical, diagnostic and therapeutic context of PDZK1IP1

• As revealed by immunofluorescence, MAP17 was abundant in S1 but almost absent in S3 segments [11].
• Using in situ hybridization, we demonstrated that MAP17 and PDZK1 mRNAs are markedly up-regulated in human carcinomas [13].

References