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1.  STAT5 N-domain deleted isoforms are naturally occurring hypomorphs partially rescued in hematopoiesis by transgenic Bcl-2 expression 
Signal transducer and activator of transcription 5 (STAT5) is a critical regulator of normal and leukemic lympho-myeloid development through activation downstream of early-acting cytokines, their receptors, and JAKs. Truncation of STAT5 can be mediated through alternative translation initiation from an internal start codon giving rise to N-terminally deleted isoforms. To determine whether these isoforms could be detected naturally in normal murine tissues, Western blot analyses were performed on heart, lung, brain, spleen, liver, and kidney. Relative expression of full-length to truncated STAT5 was variable among tissues. Since we have previously demonstrated that STAT5abΔN lacks the ability to effectively upregulate pro-survival signals and bcl-2 expression, we used a transgenic mouse approach to next determine whether constitutive expression of human Bcl-2 in STAT5abΔN/ΔN mouse hematopoietic cells could restore normal hematopoiesis. Transgenic H2K-Bcl-2 expression in hypomorphic STAT5abΔN/ΔN mice largely rescued peripheral B and T lymphocyte numbers whereas multilineage donor contribution was only rescued to levels about 10% of normal. At the hematopoietic stem cell level, direct competitive repopulation with H2K-Bcl-2/STAT5abΔN/ΔN against STAT5abΔN/ΔN competitor showed a corrective effect of Bcl-2 expression whether the STAT5abΔN/ΔN genotype was competed as the donor or as the host versus H2K-Bcl-2/STAT5abΔN/ΔN genotype bone marrow cells. Therefore, STAT5abΔN isoforms are heterogeneously expressed and lack key functional activities that can be partially rescued by adding back Bcl-2.
PMCID: PMC4165113  PMID: 25232501
Cytokine signaling; JAK/STAT; hematopoiesis; apoptosis; Bcl-2
2.  Grb2-associated binding (Gab) proteins in hematopoietic and immune cell biology 
Grb2-associated binding (Gab) scaffolding/adapter proteins are a family of three members including mammalian Gab1, Gab2, and Gab3 that are highly conserved. Since the discovery of these proteins, there has been an extensive amount of work done to better understand Gab functional roles in multiple signaling pathways, typically acting as a downstream effectors of receptor-tyrosine kinase (RTK)-triggered signal transduction. In addition to their participation in hematopoiesis, Gabs play important roles in regulation of immune response and in also in cancer cell signaling. Gabs may play complex roles and thus a complete understanding of their interactions and how they modulate hematopoietic and immune cell biology remains to be determined. This review will cover the most recent findings including the involvement of Gabs in disease development and signaling which will be important for design of future therapeutic interventions.
PMCID: PMC3232456  PMID: 22163099
Adapter protein; cytokine signaling; Grb2-associated binding protein; Gab; receptor tyrosine kinase; cancer signaling

Results 1-2 (2)