PMID- 35646067
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 13
DP  - 2022
TI  - Tyrosine Phosphorylation Profiling Revealed the Signaling Network Characteristics 
      of CAMKK2 in Gastric Adenocarcinoma.
PG  - 854764
LID - 10.3389/fgene.2022.854764 [doi]
LID - 854764
AB  - Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a 
      serine/threonine protein kinase which functions via the calcium-triggered 
      signaling cascade with CAMK1, CAMK4, and AMPKalpha as the immediate downstream 
      substrates. CAMKK2 is reported to be overexpressed in gastric cancer; however, 
      its signaling mechanism is poorly understood. We carried out label-free 
      quantitative tyrosine phosphoproteomics to investigate tyrosine-mediated 
      molecular signaling associated with CAMKK2 in gastric cancer cells. Using a 
      high-resolution Orbitrap Fusion Tribrid Fourier-transform mass spectrometer, we 
      identified 350 phosphotyrosine sites mapping to 157 proteins. We observed 
      significant alterations in 81 phosphopeptides corresponding to 63 proteins upon 
      inhibition of CAMKK2, among which 16 peptides were hyperphosphorylated 
      corresponding to 13 proteins and 65 peptides were hypophosphorylated 
      corresponding to 51 proteins. We report here that the inhibition of CAMKK2 leads 
      to changes in the phosphorylation of several tyrosine kinases such as PKP2, PTK2, 
      EPHA1, EPHA2, PRKCD, MAPK12, among others. Pathway analyses revealed that 
      proteins are differentially phosphorylated in response to CAMKK2 inhibition 
      involved in focal adhesions, actin cytoskeleton, axon guidance, and signaling by 
      VEGF. The western blot analysis upon inhibition and/or silencing of CAMKK2 
      revealed a decrease in phosphorylation of PTK2 at Y925, c-JUN at S73, and STAT3 
      at Y705, which was in concordance with the mass spectrometry data. The study 
      indicates that inhibition of CAMKK2 has an anti-oncogenic effect in gastric cells 
      regulating phosphorylation of STAT3 through PTK2/c-JUN in gastric cancer.
CI  - Copyright (c) 2022 Najar, Arefian, Sidransky, Gowda, Prasad, Modi and Chatterjee.
FAU - Najar, Mohd Altaf
AU  - Najar MA
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be 
      University), Mangalore, India.
FAU - Arefian, Mohammad
AU  - Arefian M
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be 
      University), Mangalore, India.
FAU - Sidransky, David
AU  - Sidransky D
AD  - Department of Oncology and Otolaryngology-Head and Neck Surgery, Johns Hopkins 
      University School of Medicine, Baltimore, MD, United States.
FAU - Gowda, Harsha
AU  - Gowda H
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be 
      University), Mangalore, India.
AD  - Institute of Bioinformatics, International Technology Park, Bangalore, India.
AD  - Manipal Academy of Higher Education (MAHE), Manipal, India.
FAU - Prasad, T S Keshava
AU  - Prasad TSK
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be 
      University), Mangalore, India.
FAU - Modi, Prashant Kumar
AU  - Modi PK
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be 
      University), Mangalore, India.
FAU - Chatterjee, Aditi
AU  - Chatterjee A
AD  - Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be 
      University), Mangalore, India.
AD  - Institute of Bioinformatics, International Technology Park, Bangalore, India.
LA  - eng
PT  - Journal Article
DEP - 20220513
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC9136244
OTO - NOTNLM
OT  - CAMKK2
OT  - PTK2
OT  - STAT3
OT  - gastric cancer
OT  - mass spectrometry
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/02 06:00
MHDA- 2022/06/02 06:01
PMCR- 2022/05/13
CRDT- 2022/06/01 11:31
PHST- 2022/01/14 00:00 [received]
PHST- 2022/03/28 00:00 [accepted]
PHST- 2022/06/01 11:31 [entrez]
PHST- 2022/06/02 06:00 [pubmed]
PHST- 2022/06/02 06:01 [medline]
PHST- 2022/05/13 00:00 [pmc-release]
AID - 854764 [pii]
AID - 10.3389/fgene.2022.854764 [doi]
PST - epublish
SO  - Front Genet. 2022 May 13;13:854764. doi: 10.3389/fgene.2022.854764. eCollection 
      2022.