Temporal Dynamics of VEGFA-Induced VEGFR2/FAK Co-Localization Depend on SHB

Pietilä, IlkkaUppsala universitet,Institutionen för medicinsk cellbiologi,Vaskulärbiologi (författare)

Focal adhesion kinase (FAK) is essential for vascular endothelial growth factor-A (VEGFA)/VEGF receptor-2 (VEGFR2)-stimulated angiogenesis and vascular permeability. We have previously noted that presence of the Src homology-2 domain adapter protein B (SHB) is of relevance for VEGFA-stimulated angiogenesis in a FAK-dependent manner. The current study was conducted in order address the temporal dynamics of co-localization between these components in HEK293 and primary lung endothelial cells (EC) by total internal reflection fluorescence microscopy (TIRF). An early (<2.5 min) VEGFA-induced increase in VEGFR2 co-localization with SHB was dependent on tyrosine 1175 in VEGFR2. VEGFA also enhanced SHB co-localization with FAK. FAK co-localization with VEGFR2 was dependent on SHB since it was significantly lower in SHB deficient EC after VEGFA addition. Absence of SHB also resulted in a gradual decline of VEGFR2 co-localization with FAK under basal (prior to VEGFA addition) conditions. A similar basal response was observed with expression of the Y1175F-VEGFR2 mutant in wild type EC. The distribution of focal adhesions in SHB-deficient EC was altered with a primarily perinuclear location. These live cell data implicate SHB as a key component regulating FAK activity in response to VEGFA/VEGFR2.

van Mourik, DjenolanUppsala universitet,Institutionen för medicinsk cellbiologi (författare)
Tamelander, AndreasUppsala universitet,Institutionen för medicinsk cellbiologi (författare)
Kriz, VitezslavInstitute of Molecular Genetics of the CAS, 14220 Prague, Czech Republic (författare)
Claesson-Welsh, LenaUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)lcl04207 (författare)
Tengholm, Anders,1971-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)andeteng (författare)
Welsh, Michael,1957-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)michwels (författare)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

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