PMID- 10224048
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 19
DP  - 1999 May 7
TI  - SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin
      encode polyphosphoinositide phosphatases.
PG  - 12990-5
AB  - The SAC1 gene product has been implicated in the regulation of actin
      cytoskeleton, secretion from the Golgi, and microsomal ATP transport; yet its
      function is unknown. Within SAC1 is an evolutionarily conserved 300-amino acid
      region, designated a SAC1-like domain, that is also present at the amino termini 
      of the inositol polyphosphate 5-phosphatases, mammalian synaptojanin, and certain
      yeast INP5 gene products. Here we report that SAC1-like domains have intrinsic
      enzymatic activity that defines a new class of polyphosphoinositide phosphatase
      (PPIPase). Purified recombinant SAC1-like domains convert yeast lipids
      phosphatidylinositol (PI) 3-phosphate, PI 4-phosphate, and PI 3,5-bisphosphate to
      PI, whereas PI 4,5-bisphosphate is not a substrate. Yeast lacking Sac1p exhibit
      10-, 2.5-, and 2-fold increases in the cellular levels of PI 4-phosphate, PI
      3,5-bisphosphate, and PI 3-phosphate, respectively. The 5-phosphatase domains of 
      synaptojanin, Inp52p, and Inp53p are also catalytic, thus representing the first 
      examples of an inositol signaling protein with two distinct lipid phosphatase
      active sites within a single polypeptide chain. Together, our data provide a long
      sought mechanism as to how defects in Sac1p overcome certain actin mutants and
      bypass the requirement for yeast phosphatidylinositol/phosphatidylcholine
      transfer protein, Sec14p. We demonstrate that PPIPase activity is a key regulator
      of membrane trafficking and actin cytoskeleton organization and suggest signaling
      roles for phosphoinositides other than PI 4,5-bisphosphate in these processes.
      Additionally, the tethering of PPIPase and 5-phosphatase activities indicate a
      novel mechanism by which concerted phosphoinositide hydrolysis participates in
      membrane trafficking.
FAU - Guo, S
AU  - Guo S
AD  - Departments of Pharmacology and Cancer Biology and of Biochemistry, Duke
      University Medical Center, Durham, North Carolina 27710, USA.
FAU - Stolz, L E
AU  - Stolz LE
FAU - Lemrow, S M
AU  - Lemrow SM
FAU - York, J D
AU  - York JD
LA  - eng
GR  - R01-HL 55672/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Fungal Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.3.- (synaptojanin)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.56 (Inositol Polyphosphate 5-Phosphatases)
SB  - IM
MH  - Fungal Proteins/*genetics/metabolism
MH  - Humans
MH  - Inositol Polyphosphate 5-Phosphatases
MH  - Nerve Tissue Proteins/*genetics/metabolism
MH  - Phosphoric Monoester Hydrolases/*genetics/metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Saccharomyces cerevisiae/enzymology/*genetics
EDAT- 1999/05/01 00:00
MHDA- 1999/05/01 00:01
CRDT- 1999/05/01 00:00
PHST- 1999/05/01 00:00 [pubmed]
PHST- 1999/05/01 00:01 [medline]
PHST- 1999/05/01 00:00 [entrez]
AID - 10.1074/jbc.274.19.12990 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 7;274(19):12990-5. doi: 10.1074/jbc.274.19.12990.