Role of Src-family kinases and c-Abl in regulating myeloid leukocyte adhesion, migration and activation

Data inizio
31 dicembre 2010
Durata (mesi) 
36
Responsabili (o referenti locali)
Berton Giorgio

Src family tyrosine kinases play an essential role in signal transduction by different
receptors. The evidence that c-Src acts as an oncogene implicated in regulation of cell
growth and invasive capacity has been recently strengthen by the findings that an integrine-Src oncogenic unit promotes tumor progression and the acquisition of a metastatic phenotype. Studies performed in the laboratories of the applicant and of the applicant’s collaborators have established that Src-family kinases (SFKs), play an essential role in integrin-dependent myelomonocytic cell activation, movement and recruitment into tissues. More recently, we found that in myeloid cells the tyrosine kinase c-Abl interacts with the two leukocyte-specific SFKs Fgr or Hck bound to beta1 or beta2 integrins and is activated in a SFK-dependent manner. c-Abl-selective inhibitors, similarly to SFK-selective inhibitors, markedly inhibit myeloid cell migration and polarization. The main goal of this research project is to dissect mechanisms by which Src-family kinases and c-Abl crosstalk within a signaling pathway triggered by integrins and chemoattractant receptors. This objective will include studies on myeloid leukocytes, Bcr-Abl+ hematopoietic cell lines, cells from chronic myeloid leukemia (CML) patients and tumor cell lines.

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