Paxillin
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Paxillin is a
striated muscle cells, and it functions to adhere cells to the extracellular matrix
. Mutations in PXN as well as abnormal expression of paxillin protein has been implicated in the progression of various cancers.
Structure
Human paxillin is 64.5 kDa in molecular weight and 591
amino acids in length.[5]
The
focal adhesions.[8]
The
Function
Paxillin is a
focal adhesion kinase (FAK), structural proteins, such as vinculin and actopaxin, and regulators of actin organization, such as COOL/PIX and PKL/GIT. Paxillin is tyrosine-phosphorylated by FAK and Src upon integrin engagement or growth factor stimulation,[14] creating binding sites for the adapter protein Crk
.
In
cardiomyocytes with the hypertrophic agonist, phenylephrine stimulated a rapid increase in tyrosine phosphorylation paxillin, which was mediated by protein tyrosine kinases.[20]
The structural reorganization of paxillin in
cardiac hypertrophy, inducing hypertrophic cardiomyopathy, paxillin expression levels increased, suggesting a role for paxillin in both types of cardiomyopathy.[23]
Clinical significance
Paxillin has been shown to have a clinically-significant role in patients with several cancer types. Enhanced expression of paxillin has been detected in premalignant areas of
lung adenocarcinoma.[24] Mutations in PXN have been associated with enhanced tumor growth, cell proliferation, and invasion in lung cancer tissues.[25]
During tumor transformation, a consistent finding is that paxillin protein is recruited and
phosphorylated.[26] Paxillin plays a role in the MET tyrosine kinase signaling pathway, which is upregulated in many cancers.[27]
Interactions
Paxillin has been shown to
interact
with:
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000089159 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029528 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Protein sequence of human PXN (Uniprot ID: P49023)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on July 13, 2015. Retrieved July 13, 2015.
- ^ PMID 9497381.
- ^ S2CID 9744939.
- PMID 10400685.
- S2CID 9635426.
- S2CID 26269466.
- PMID 7534286.
- PMID 9785458.
- ^ PMID 2118142.
- PMID 7615549.
- S2CID 41193996.
- PMID 16533505.
- ^ PMID 17462669.
- PMID 21937583.
- PMID 17785437.
- PMID 10749882.
- PMID 12228222.
- PMID 10749567.
- PMID 19540241.
- PMID 21045234.
- PMID 18172305.
- PMID 9467941.
- PMID 20139696.
- PMID 8207093.
- PMID 7525621.
- PMID 7579684.
- PMID 8922390.
- PMID 11069756.
- S2CID 26455236.
- PMID 11134073.
- PMID 11304546.
Further reading
- Panetti TS (January 2002). "Tyrosine phosphorylation of paxillin, FAK, and p130CAS: effects on cell spreading and migration". Frontiers in Bioscience. 7 (1–3): d143-50. S2CID 35708933.
- Rose DM, Han J, Ginsberg MH (August 2002). "Alpha4 integrins and the immune response". Immunological Reviews. 186: 118–24. S2CID 37850994.
- Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M, de Jong R, Druker B, Heisterkamp N, Chen LB (December 1995). "CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells". The Journal of Biological Chemistry. 270 (49): 29145–50. PMID 7493940.
- Bergman M, Joukov V, Virtanen I, Alitalo K (February 1995). "Overexpressed Csk tyrosine kinase is localized in focal adhesions, causes reorganization of alpha v beta 5 integrin, and interferes with HeLa cell spreading". Molecular and Cellular Biology. 15 (2): 711–22. PMID 7529872.
- Schaller MD, Otey CA, Hildebrand JD, Parsons JT (September 1995). "Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains". The Journal of Cell Biology. 130 (5): 1181–7. PMID 7657702.
- Yoshida M, Westlin WF, Wang N, Ingber DE, Rosenzweig A, Resnick N, Gimbrone MA (April 1996). "Leukocyte adhesion to vascular endothelium induces E-selectin linkage to the actin cytoskeleton". The Journal of Cell Biology. 133 (2): 445–55. PMID 8609175.
- Salgia R, Sattler M, Pisick E, Li JL, Griffin JD (February 1996). "p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl". Experimental Hematology. 24 (2): 310–3. PMID 8641358.
- Salgia R, Pisick E, Sattler M, Li JL, Uemura N, Wong WK, Burky SA, Hirai H, Chen LB, Griffin JD (October 1996). "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". The Journal of Biological Chemistry. 271 (41): 25198–203. PMID 8810278.
- Retta SF, Barry ST, Critchley DR, Defilippi P, Silengo L, Tarone G (December 1996). "Focal adhesion and stress fiber formation is regulated by tyrosine phosphatase activity". Experimental Cell Research. 229 (2): 307–17. PMID 8986614.
- Mazaki Y, Hashimoto S, Sabe H (March 1997). "Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins". The Journal of Biological Chemistry. 272 (11): 7437–44. PMID 9054445.
- Hiregowdara D, Avraham H, Fu Y, London R, Avraham S (April 1997). "Tyrosine phosphorylation of the related adhesion focal tyrosine kinase in megakaryocytes upon stem cell factor and phorbol myristate acetate stimulation and its association with paxillin". The Journal of Biological Chemistry. 272 (16): 10804–10. PMID 9099734.
- Ostergaard HL, Lou O, Arendt CW, Berg NN (March 1998). "Paxillin phosphorylation and association with Lck and Pyk2 in anti-CD3- or anti-CD45-stimulated T cells". The Journal of Biological Chemistry. 273 (10): 5692–6. PMID 9488700.
- Fernandez R, Suchard SJ (May 1998). "Syk activation is required for spreading and H2O2 release in adherent human neutrophils". Journal of Immunology. 160 (10): 5154–62. S2CID 22362259.
- Lewis JM, Schwartz MA (June 1998). "Integrins regulate the association and phosphorylation of paxillin by c-Abl". The Journal of Biological Chemistry. 273 (23): 14225–30. PMID 9603926.
- Ganju RK, Munshi N, Nair BC, Liu ZY, Gill P, Groopman JE (July 1998). "Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells". Journal of Virology. 72 (7): 6131–7. PMID 9621077.
- Deakin NO, Turner CE (August 2008). "Paxillin comes of age". Journal of Cell Science. 121 (Pt 15): 2435–44. PMID 18650496.
External links
- MBInfo: Paxillin
- Paxillin Info with links in the Cell Migration Gateway Archived December 11, 2014, at the Wayback Machine
- Paxillin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P49023 (Human Paxillin) at the PDBe-KB.
- Overview of all the structural information available in the PDB for UniProt: Q8VI36 (Mouse Paxillin) at the PDBe-KB.