FAK+ and PYK2/CAKβ, two related tyrosine kinases highly expressed in the central nervous system: similarities and differences in the expression pattern

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Abstract
Focal adhesion kinase (FAK) and proline‐rich tyrosine kinase 2/cell adhesion kinase β (PYK2/CAKβ) are related, non‐receptor, cytoplasmic tyrosine kinases, highly expressed in the central nervous system (CNS). In addition, FAK+ is a splice isoform of FAK containing a 3‐amino acid insertion in the carboxy‐terminal region. In rat hippocampal slices, FAK+ and PYK2/CAKβ are differentially regulated by neurotransmitters and depolarization. We have studied the regional and cellular distribution of these kinases in adult rat brain and during development. Whereas PYK2/CAKβ expression increased with postnatal age and was maximal in the adult, FAK+ levels were stable. PYK2/CAKβ mRNAs, detected by in situ hybridization, were expressed at low levels in the embryonic brain, and became very abundant in the adult forebrain. Immunocytochemistry of the adult brain showed a widespread neuronal distribution of FAK+ and PYK2/CAKβ immunoreactivities (ir). PYK2/CAKβ appeared to be particularly abundant in the hippocampus. In hippocampal neurons in culture at early stages of development, FAK+ and PYK2/CAKβ were enriched in the perikarya and growth cones. FAK+ extended to the periphery of the growth cones tips, whereas PYK2/CAKβ appeared to be excluded from the lamellipodia. During the establishment of polarity, a proximal‐distal gradient of increasing PYK2/CAKβ‐ir could be observed in the growing axon. In most older neurons, FAK+‐ir was confined to the cell bodies, whereas PYK2/CAKβ‐ir was also present in the processes. In vitro and in vivo, a subpopulation of neurons displayed neurites with intense FAK+‐ir. Thus, FAK+ and PYK2/CAKβ are differentially regulated during development yet they are both abundantly expressed in the adult brain, with distinctive but overlapping distributions.