With No Lysine 1 (WNK1): A Potential Regulator of The Lysosomal Degradation Pathway

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Title: With No Lysine 1 (WNK1): A Potential Regulator of The Lysosomal Degradation Pathway
Author: Lenertz, Lisa Yvonne
Abstract: With no Lysine (K ) 1 (WNK1 ) is an atypical serine /threonine protein kinase that has its catalytic lysine positioned in a unique location . This kinase , along with another member of the WNK family , WNK4 , has been genetically linked to pseudohypoaldosteronism type II (PHAII ) , which is characterized by both hypertension and hyperkalemia . Several groups have used reconstitution assays in Xenopus oocytes and mammalian cell lines to show WNKs regulate the surface expression and /or activity of various ion transporters and channels , including the epithelial sodium channel (ENaC ) and the sodium chloride co -transporter (NCCT ) . Although the mechanisms for regulating these cell surface proteins are not well defined , it appears that WNKs may modulate the intracellular trafficking of these channels and transporters . To help define the mechanisms WNK1 utilizes to influence blood pressure and to characterize this kinase biochemically , I performed a WNK1 kinase activation screen and a WNK1 yeast -two -hybrid screen . I have shown that WNK1 kinase activity increases in response to osmotic stress , which may imply its kinase activity is important for regulating ion homeostasis in response to a change in cell volume . I have also shown that a proline -rich region of WNK1 interacts with vacuolar protein sorting 4a (VPS4a ) , an ATPase that helps sort cargo from the plasma membrane to lysosomes . Cells expressing a VPS4 ATP -hydrolysis mutant trap cargo from the cell surface in an aberrant endosomal structure , slowing protein degradation via the lysosomal pathway . I hypothesize that WNK1 delivers cargo to VPS4a to facilitate the degradation of plasma membrane proteins .
URI: http : / /hdl .handle .net /2152 .5 /381
Date: 2007-05-22

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With No Lysine 1 (WNK1): A Potential Regulator of The Lysosomal Degradation Pathway. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /381 .

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