Focal adhesion kinase splice variants maintain primitive acute myeloid leukemia cells through altered Wnt signaling.

Focal adhesion kinase (FAK) activity contributes to many advanced cancer phenotypes, but little is known about its role in human acute myeloid leukemia (AML). Here, we show that FAK splice variants are abnormally expressed in the primitive leukemic cells of poor prognosis AML patients. In the CD34(+) 38(-) 123(+) long-term culture-initiating cell-enriched leukemic cells of these patients, FAK upregulates expression of Frizzled-4 and phosphorylates Pyk2 to enable the required association of Pyk2 with the Wnt5a/Frizzled-4/LRP5 endocytosis complex and downstream activation of β-catenin, thereby replacing the Wnt3a-controlled canonical pathway used by normal hematopoietic stem cells.

[Neuronal isoforms of Src, Fyn and Lck tyrosine kinases: A specific role for p56lckN in neuron protection].

The two main tyrosine kinases (TK) in the brain are p60Src and p59Fyn, expressed as specific isoforms (p60SrcNI, p60SrcNI+NII and p59fynB). They play a pivotal role in some major processes such as neuronal growth and myelinisation. Another member of this TK family was then reported in brain, the p56lck.

Organization and post-transcriptional processing of focal adhesion kinase gene.

Background: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase critical for processes ranging from embryo development to cancer progression. Although isoforms with specific molecular and functional properties have been characterized in rodents and chicken, the organization of FAK gene throughout phylogeny and its potential to generate multiple isoforms are not well understood. Here, we study the phylogeny of FAK, the organization of its gene, and its post-transcriptional processing in rodents and human.

[Expression of the p56lck by colon tumors: a marker of their invasive capacity?].

Since its discovery in murine thymoma in 1982, the p56lck (lymphocyte cellular kinase) has been shown to be a pivotal enzyme to both maturation of thymocytes and activation and proliferation of peripheral lymphocytes. The p56lck sequence appeared highly homologous to that of the oncogene p60c-src as did its exon-intron organisation. These data have suggested the lck gene originates from the ancestral src gene by the exon-shuffling mechanism.

The exon 7-spliced Lck isoform in T lymphocytes: a potential regulator of p56lck signaling pathways.

The protein-tyrosine kinase p56lck is the product of the lck gene. It plays a pivotal role in T-lymphocyte activation and thymocyte development, as indicated by the defective immune responses of lck-/- mice. We have demonstrated that an exon 7-deleted lck mRNA is produced by alternative splicing in all human cells expressing the lck gene.