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Endoplasmic reticulum stress‐inducible protein GRP94 is associated with an Mg 2+ ‐dependent serine kinase activity modulated by Ca 2+ and GRP78/BiP
Author(s) -
Ramakrishnan Meera,
Schönthal Axel H.,
Lee Amy S.
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199702)170:2<115::aid-jcp3>3.0.co;2-r
Subject(s) - endoplasmic reticulum , autophosphorylation , protein kinase a , mitogen activated protein kinase kinase , kinase , casein kinase 2, alpha 1 , biochemistry , casein kinase 2 , unfolded protein response , microbiology and biotechnology , ask1 , map kinase kinase kinase , phosphorylation , biology , chemistry
The 94‐kDa glucose‐regulated protein (GRP94) is a glycoprotein in the endoplasmic reticulum (ER). It has been characterized as a Ca 2+ ‐binding protein and a molecular chaperone. In this report we show that highly purified GRP94 exhibits an active Mg 2+ ‐dependent serine kinase activity (termed 94‐kinase). The 94‐kinase can be recovered from ER membrane fractions and is able to phosphorylate both the constitutive and stress‐induced forms of GRP94, correlating with their induction kinetics. The 94‐kinase activity is distinct from casein kinase II. In contrast to the heat‐stable, Ca 2+ ‐dependent autophosphorylation activity recently reported for GRP94, the labile 94‐kinase activity is inhibited by Ca 2+ . We determined that the phosphopeptide map of in vitro phosphorylated GRP94 by the 94‐kinase resembles that of the in vivo phosphorylated GRP94. Further, the 94‐kinase activity can be specifically stimulated by GRP78, a coregulated protein in the ER known to interact with GRP94. J. Cell. Physiol. 170:115–129, 1997. © 1997 Wiley‐Liss, Inc.