New Techniques Using Phosphoserine Antibodies

Thu, 08/16/2012 - 12:51

Phosphoserine, the phosphorylated modification of the amino acid serine, is a central post-translational modification within a cell for many biological and biomedical processes. The phosphorylation of specifically four residue types - histidine, serine, threonine, and tyrosine occurs both within the cell as well as at the cell surface. This exquisitely controlled regulatory system controls a vast number of intertwined and interconnected downstream signaling pathways and cascades.  The signal transduction networks that rely on phosphorylation are very complex, such that multiple types of phosphorylation often occur within any one given protein, at multiple sites and hotspot areas. There exist a great number of techniques and technologies for phosphoamino acid detection and study, each with strengths as well as limitations, as reviewed by Yan, et. al. (1). Powerful new methods using phosphoserine antibodies are emerging, such as the development of a high-density peptide microarray for profiling 1,110+ serine/threonine and 290+ tyrosine protein kinase substrates (2). This novel array detected many unique, highly reactive and specific peptides and is a step toward high-throughput discovery of kinase substrates. Woolley, et. al. used phosphoserine antibodies in immunohistochemical studies to evaluate the use of the Y-box binding protein1 (YB1) as a prognostic marker for breast cancer (3). Despite the prevalence of phosphoserine in the literature, new discoveries are still being made – phosphoserine antibodies allowed Wang’s group to identify serine phosphophorylation of NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) as a tumorigenic-driving event for this oncoprotein (4). Therapeutic approaches exploiting phosphoserine antibodies include pathway-based biomarker phosphoprofiling as biomarkers for monitoring phosphatidylinositol 3-kinase (PI3K) inhibitor activity and effectiveness in prostate and breast cancers(5) and tau immunotherapy in Alzheimer’s disease (6).

  1. PMID: 9652109
  2. PMID: 20615195
  3. PMID: 21695211
  4. PMID: 21045017
  5. PMID: 20686178
  6. PMID: 22272619

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