RGSZ1, a G(z)-selective rgs protein in brain: Structure, membrane association, regulation by Gα(z) phosphorylation, and relationship to a G(z) gtpase-activating protein subfamily

Jun Wang, Axel Ducret, Yaping Tu, Tohru Kozasa, Ruedi Aebersold, Elliott M. Ross

Research output: Contribution to journalArticle

127 Scopus citations


We cloned the cDNA for human RGSZ1, the major G(z)-selective GTPase- activating protein (GAP) in brain (Wang, J., Tu, Y., Woodson, J., Song, X., and Ross, E. M. (1997) J. Biol. Chem. 272, 5732-5740) and a member of the RGS family of G protein GAPs. Its sequence is 83% identical to RET-RGS1 (except its N-terminal extension) and 56% identical to GAIP. Purified, recombinant RGSZ1, RET-RGS1, and GAIP each accelerated the hydrolysis of Gα(z)-GTP over 400-fold with K(m) values of ~2 nM. RGSZ1 was 100-fold selective for Gα(z) over Gα1, unusually specific among RGS proteins. Other enzymological properties of RGSZ1, brain G(z) GAP, and RET-RGS1 were identical; GAIP differed only in Mg2+ dependence and in its slightly lower selectivity for Gα(z). RGSZ1, RET-RGS1, and GAIP thus define a subfamily of G(z) GAPs within the RGS proteins. RGSZ1 has no obvious membrane-spanning region but is tightly membrane-bound in brain. Its regulatory activity in membranes depends on stable bilayer association. When co-reconstituted into phospholipid vesicles with G(z) and m2 muscarinic receptors, RGSZ1 increased agonist- stimulated GTPase >15-fold with EC50 <12 nM, but RGSZ1 added to the vesicle suspension was <0.1% as active. RGSZ1, RET-RGS1, and GAIP share a cysteine string sequence, perhaps targeting them to secretory vesicles and allowing them to participate in the proposed control of secretion by G(z). Phosphorylation of Gα(z) by protein kinase C inhibited the GAP activity of RGSZ1 and other RGS proteins, providing a mechanism for potentiation of G(z) signaling by protein kinase C.

Original languageEnglish (US)
Pages (from-to)26014-26025
Number of pages12
JournalJournal of Biological Chemistry
Issue number40
StatePublished - Oct 2 1998


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this