PMID- 23105102
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 1
DP  - 2013 Jan 4
TI  - Dynamic phosphorylation of tyrosine 665 in pseudopodium-enriched atypical kinase 
      1 (PEAK1) is essential for the regulation of cell migration and focal adhesion 
      turnover.
PG  - 123-31
LID - 10.1074/jbc.M112.410910 [doi]
AB  - Pseudopodium-enriched atypical kinase 1 (PEAK1) is a recently described tyrosine 
      kinase that associates with the actin cytoskeleton and focal adhesion (FA) in 
      migrating cells. PEAK1 is known to promote cell migration, but the responsible 
      mechanisms remain unclear. Here, we show that PEAK1 controls FA assembly and 
      disassembly in a dynamic pathway controlled by PEAK1 phosphorylation at Tyr-665. 
      Knockdown of endogenous PEAK1 inhibits random cell migration. In PEAK1-deficient 
      cells, FA lifetimes are decreased, FA assembly times are shortened, and FA 
      disassembly times are extended. Phosphorylation of Tyr-665 in PEAK1 is essential 
      for normal PEAK1 localization and its function in the regulation of FAs; however, 
      constitutive phosphorylation of PEAK1 Tyr-665 is also disruptive of its function, 
      indicating a requirement for precise spatiotemporal regulation of PEAK1. Src 
      family kinases are required for normal PEAK1 localization and function. Finally, 
      we provide evidence that PEAK1 promotes cancer cell invasion through Matrigel by 
      a mechanism that requires dynamic regulation of Tyr-665 phosphorylation.
FAU - Bristow, Jeanne M
AU  - Bristow JM
AD  - Department of Pathology and Moores Cancer Center, University of California at San 
      Diego, La Jolla, California 92093, USA.
FAU - Reno, Theresa A
AU  - Reno TA
FAU - Jo, Minji
AU  - Jo M
FAU - Gonias, Steven L
AU  - Gonias SL
FAU - Klemke, Richard L
AU  - Klemke RL
LA  - eng
GR  - R01 CA097022/CA/NCI NIH HHS/United States
GR  - R01 HL060551/HL/NHLBI NIH HHS/United States
GR  - CA097022/CA/NCI NIH HHS/United States
GR  - HL060551/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121026
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Paxillin)
RN  - 0 (Proteoglycans)
RN  - 119978-18-6 (matrigel)
RN  - 42HK56048U (Tyrosine)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.10.1 (PEAK1 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Collagen/chemistry
MH  - Drug Combinations
MH  - Focal Adhesions/*chemistry
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Laminin/chemistry
MH  - Paxillin/metabolism
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/*chemistry
MH  - Proteoglycans/chemistry
MH  - Time Factors
MH  - Tyrosine/*chemistry
MH  - src-Family Kinases/metabolism
PMC - PMC3537006
EDAT- 2012/10/30 06:00
MHDA- 2013/03/01 06:00
PMCR- 2014/01/04
CRDT- 2012/10/30 06:00
PHST- 2012/10/30 06:00 [entrez]
PHST- 2012/10/30 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
PHST- 2014/01/04 00:00 [pmc-release]
AID - S0021-9258(20)65317-0 [pii]
AID - M112.410910 [pii]
AID - 10.1074/jbc.M112.410910 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Jan 4;288(1):123-31. doi: 10.1074/jbc.M112.410910. Epub 2012 
      Oct 26.