PMID- 10022920
OWN - NLM
STAT- MEDLINE
DCOM- 19990325
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 3
DP  - 1999 Mar
TI  - Identification of a new Pyk2 target protein with Arf-GAP activity.
PG  - 2338-50
AB  - Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled
      receptors and by extracellular signals that elevate intracellular Ca2+
      concentration. We have identified a new Pyk2 binding protein designated Pap. Pap 
      is a multidomain protein composed of an N-terminal alpha-helical region with a
      coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain,
      an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain.
      We demonstrate that Pap forms a stable complex with Pyk2 and that activation of
      Pyk2 leads to tyrosine phosphorylation of Pap in living cells. Immunofluorescence
      experiments demonstrate that Pap is localized in the Golgi apparatus and at the
      plasma membrane, where it is colocalized with Pyk2. In addition, in vitro
      recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards 
      the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Addition of
      recombinant Pap protein to Golgi preparations prevented Arf-dependent generation 
      of post-Golgi vesicles in vitro. Moreover, overexpression of Pap in cultured
      cells reduced the constitutive secretion of a marker protein. We propose that Pap
      functions as a GAP for Arf and that Pyk2 may be involved in regulation of
      vesicular transport through its interaction with Pap.
FAU - Andreev, J
AU  - Andreev J
AD  - Department of Pharmacology, New York University Medical Center, New York, New
      York 10016, USA.
FAU - Simon, J P
AU  - Simon JP
FAU - Sabatini, D D
AU  - Sabatini DD
FAU - Kam, J
AU  - Kam J
FAU - Plowman, G
AU  - Plowman G
FAU - Randazzo, P A
AU  - Randazzo PA
FAU - Schlessinger, J
AU  - Schlessinger J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (ASAP1 protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Asap1 protein, mouse)
RN  - 0 (Carrier Proteins)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
RN  - EC 2.7.10.2 (Ptk2b protein, mouse)
RN  - EC 2.7.10.2 (Ptk2b protein, rat)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factor 1)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factors)
RN  - EC 3.6.5.2 (Arf5 protein, mouse)
RN  - EC 3.6.5.2 (Arf5 protein, rat)
SB  - IM
MH  - ADP-Ribosylation Factor 1
MH  - ADP-Ribosylation Factors
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Carrier Proteins/genetics/*physiology
MH  - Cell Line, Transformed
MH  - Focal Adhesion Kinase 2
MH  - GTP-Binding Proteins/*metabolism
MH  - GTPase-Activating Proteins
MH  - Golgi Apparatus/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Fluid
MH  - Mice
MH  - Molecular Sequence Data
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Proteins/*metabolism
MH  - Proto-Oncogene Proteins pp60(c-src)/metabolism
MH  - Rabbits
MH  - Rats
MH  - Tyrosine/metabolism
MH  - *src Homology Domains
PMC - PMC84026
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1128/mcb.19.3.2338 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Mar;19(3):2338-50. doi: 10.1128/mcb.19.3.2338.