CLONING OF FOCAL ADHESION KINASE, PP125(FAK), FROM RAT-BRAIN REVEALS MULTIPLE TRANSCRIPTS WITH DIFFERENT PATTERNS OF EXPRESSION

Focal adhesion kinase (pp125(FAK), or FAK) is a cytoplasmic tyrosine k inase enriched in focal adhesions. We have screened a rat striatum cDN A library with a PCR-amplified cDNA probe specific for FAK messenger. Sequencing of multiple clones revealed the existence of three differen t 5'-leader sequences resulting from the combination of 5 conserved bo xes. One of them contains a potential alternative initiation site, 78 base pairs upstream of that previously described. Another is 89% ident ical to a human genomic sequence located on chromosome 3. Most positiv e clones contained an insertion coding for three amino acids (Pro-Trp- Arg) in the region responsible for focal adhesion targeting. We propos e 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 hybri dization with specific primers and probes. The different 5'-leader seq uences were always found in the same proportions. In contrast, FAK + m RNA was found at very low levels in non-nervous tissues, whereas it wa s highly expressed in all brain regions. In cells in culture, it was p resent in astrocytes and enriched in neurons. These results demonstrat e the existence of multiple forms of FAK transcript and protein, one o f which, FAK +, may play a specific role in the nervous system.