Figure 8.

Proposed role for SrcFK and FAK in bronchoconstrictor or depolarization‐induced ASM contraction, based on the results of the current study and existing literature. (A) GPCR activate both SrcFK and FAK, presumably via interaction with heterotrimeric G‐protein sub‐units (e.g. Gα_q, Gα_12/13 or Gβγ) or downstream signalling molecules. Activated SrcFK forms two distinct sub‐populations: one FAK‐independent and one FAK‐dependent. (B) FAK‐independent SrcFK induces Rho‐kinase to phosphorylate MYPT‐1, thus enhancing myosin light‐chain phosphorylation (P‐MLC) through inhibition of myosin light‐chain phosphatase (MLCP). SrcFK are perhaps activating Rho‐kinase via the tyrosine phosphorylation of RhoA‐associated proteins such as RhoGEFs. (C) A FAK/Src complex may be mediating store‐operated and/or receptor‐operated Ca²⁺ entry (SOCE/ROCE) via the tyrosine phosphorylation of TRP channels, or associated signalling proteins, such as STIM1, in association with DAG. (D) FAK is also independently enhancing voltage‐operated Ca²⁺ entry (VOCE), perhaps via direct phosphorylation of voltage‐dependent Ca²⁺ channels, in response to the additional stimulus of stretch or cellular adhesion, via integrin engagement.