Phosphorylation sites of HER2/c-erbB-2: role in cell growth and in disease.
The protein kinase c-erbB-2 belongs to the family of receptor tyrosine kinase and is involved in oncogenesis. The present study predicts different phosphorylation sites of HER2/c-erbB-2 which are important in preventing or developing cancer, especially breast cancer. Sequence homology showed highest homology (77%) with epidermal growth factor receptor kinase domain. According to PROSITE search result, active sites of c-erbB-2 are N-lobe (glycine rich phosphate binding loop). Catalytic loop with presumptive catalytically active of Asp108 is phosphorylated by tyrosine protein kinase. A-loop, activation loop, becomes phosphorylated and activates the substrate binding. The study strengthens our knowledge regarding HER2 signaling by the detection of uncharacterized signaling proteins, establishing phosphorylation of an activation loop and helps us to make assumptions about the role of such previously unidentified proteins. On the basis of importance of HER2 in breast cancer as well as in other diseases, this study provides fruitful information for designing new therapeutic strategies.
Department of Biochemistry, Fatima Jinnah Medical College, Lahore, Pakistan.
Rukhshan
R
Khurshid
Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan.
Mahjabeen
M
Saleem
Department of Biochemistry, Gujranwala Medical College, Gujranwala, Pakistan.
Gul-e-Raana
Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan.
Muhammad Saleem
MS
Akhthar
D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D017433:Protein Structure, Secondary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*
D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human