Cloning of focal adhesion kinase, pp125FAK, from rat brain reveals multiple transcripts with different patterns of expression.

Focal adhesion kinase (pp125FAK, or FAK) is a cytoplasmic tyrosine kinase enriched in focal adhesions. We have screened a rat striatum cDNA library with a PCR-amplified cDNA probe specific for FAK messenger. Sequencing of multiple clones revealed the existence of three different 5'-leader sequences resulting from the combination of 5 conserved boxes. One of them contains a potential alternative initiation site, 78 base pairs upstream of that previously described. Another is 89% identical to a human genomic sequence located on chromosome 3. Most positive clones contained an insertion coding for three amino acids (Pro-Trp-Arg) in the region responsible for focal adhesion targeting. We propose to name this variant of the protein FAK +. The pattern of expression of the multiple forms of FAK was studied by RT-PCR and Southern hybridization with specific primers and probes. The different 5'-leader sequences were always found in the same proportions. In contrast, FAK + mRNA was found at very low levels in non-nervous tissues, whereas it was highly expressed in all brain regions. In cells in culture, it was present in astrocytes and enriched in neurons. These results demonstrate the existence of multiple forms of FAK transcript and protein, one of which, FAK +, may play a specific role in the nervous system.