Bilateral adrenal cortical rests: An interesting innocuous intruder in the fallopian tubes.

ABSTRACT: Ectopic adrenal rests refer to the presence of adrenal tissue outside its normal anatomical location and are usually discovered incidentally on microscopic examination. Literature suggests its occurrence in diverse extrarenal sites, like the genitourinary system and pelvis. Our case describes the rare occurrence of ectopic adrenal rests in the walls of bilateral fallopian tubes of a 43-year-old female patient who presented with a complaint of heavy menstrual bleeding. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Gross examination revealed adenomyosis with multiple fibroids, and the same was confirmed on microscopy. Additionally, the finding of a well-encapsulated lesion on the walls of both tubes made us relook at the fallopian tubes, which showed a small bright yellow area measuring less than 0.3 cm in the walls, which was consistent with ectopic adrenal rests after ruling out the morphological differentials of Walthard cell nests, aggregates of foamy histiocytes, metastatic renal clear cell carcinoma, displaced ovarian luteinized theca cells, heterotopia of ovarian hilus cells. Immunohistochemistry showed positivity for Melan A and CK7 was negative. The present case helps in investigating the lesser-explored aspect of adrenal rest pathology. It also reiterates need for detailed observation of fallopian tubectomy specimens by pathologists during grossing to avoid overlooking of potentially intriguing entities.

Copepoda community imprints the continuity of the oceanic and shelf oxygen minimum zones along the west coast of India.

The largest continental shelf Oxygen Minimum Zone (OMZ) in the world is formed along the Indian western shelf in the eastern Arabian Sea during the Southwest Monsoon [(SWM); June-September], which is a natural pollution event associated with the coastal upwelling. This study examines the composition, abundance, and distribution of copepods during the Northeast Monsoon [(NEM); November to February] and SWM in 50 m depth zones along the Indian western shelf in the eastern Arabian Sea. The NEM was characterised by warm, stratified, and low-salinity waters in the southeast Arabian Sea and cold, high-salinity, and well-mixed waters in the northeastern Arabian Sea. During the SWM, cold and Dissolved Oxygen (DO) deficient waters (<22 µM/0.5 ml L-1), which are the signs of coastal upwelling, were evident all along the study zone, but with more intensity off Kochi, Mangalore, and Goa in the south than off Mumbai and Okha in the north. The zooplankton total biomass and abundance showed seasonality with a general decrease during the SWM (av. 3.68 ± 1.29 ml m-3 and av. 5711 ± 3096 Ind. m-3, respectively) compared to the NEM (av. 7.37 ± 2.17 ml m-3 and av. 14,473 ± 4966 Ind. m-3, respectively). At the same time, the abundance of Polychaeta and Siphonophora showed an increase during the SWM (av. 1187 ± 1055 Ind. m-3 and av. 169 ± 119 Ind. m-3, respectively), probably a result of the DO deficient waters associated with upwelling. Two striking seasonal features in Copepoda community were evident in this study: (a) a compositional shift from Cyclopoida dominant during the NEM to Calanoida dominant during the SWM, and (b) the coastal OMZ along the Indian western shelf during the SWM was dominated by Calanoida, which include oceanic OMZ species such as Pleuromamma indica, Lucicutia flavicornis, L.paraclausii, Eucalanus elongatus, Subeucalanus pileatus, S.subcrassus, and Clausocalanus furcatus. This forms a clear imprint for the extension of the oceanic OMZ into nearshore waters during the SWM due to coastal upwelling.

Outcome of Management of Mandibular Sub condylar Fractures Based on Classification System Using Cone-Beam Computed Tomography.

Purpose: The purpose of this study is to determine the amount of ramal height shortening and degree of displacement of sub condylar fracture that should be considered for effective management of mandibular sub condylar fractures using cone-beam computed tomography. Patients and Methods: A prospective study of forty-two patients, who presented with unilateral sub condylar fracture was done. All patients were classified into Class I, II and III based on the degree of displacement of fractured segment and amount of ramal height shortening measured using cone-beam computed tomography. The treatment protocol was closed reduction and maxillomandibular fixation for Class I patients and open reduction and internal fixation for Class II and III patients. Outcomes of treatment were measured postoperatively 2 weeks, 1 and 3 months clinically. The variables, such as mouth opening, lateral and protrusive movements, deviation, pain and occlusion were studied. Results: Among forty-two patients, twenty had Class I fractures, twelve had Class II fractures and ten had Class III fractures. Overall, no statistically significant differences were found between Class I and Class II groups in terms of functional outcomes and there were statistically significant differences between Class I and III groups. Class I fractures can be considered for closed method and open reduction is recommended for Class II and III fractures. The sample was composed of 42 patients grouped as follows: Class I (n = 20), Class II (n = 12), and Class III (n = 10) for treatment of sub condylar fractures. There were no significant differences between the three groups for the study variables at baseline, except for mouth opening and pain. There was significant difference in mouth opening between Class I and III cases (p 0.001) and insignificant difference in mouth opening in Class I and II cases (p 0.98). Persistent pain was elicited more in surgical Class II and III (n = 5) than non-surgical cases Class I (n = 0) on 3 months follow-up. Conclusion: The study emphasises on use of three-dimensional diagnostic modality like cone-beam computed tomography for accurately classifying sub condylar fractures. The results favour closed reduction for mildly displaced Class I cases and surgical management of significantly displaced Class III fractures. The need for open reduction for Class II patients classified using CBCT is negligible assessing risks associated with surgical procedure which is contradictory to our protocol which requires a further comparative evaluation among Class II group.

Microplastics in copepods reflects the manmade flow restrictions in the Kochi backwaters, along the southwest coast of India.

This baseline study on microplastics (MPs) in calanoid copepods in the Kochi backwaters (KBW), India's largest estuary system on the west coast, focuses on (a) the spatiotemporal variations of MPs with the seasonal hydrography setting, and (b) how man-made flow restrictions of a large saltwater barrage contribute to MPs in copepods and their potential to transfer to higher trophic levels. This study found that MPs in copepods in the KBW ranged from av. 0.01 ± 0.014 to 0.11 ± 0.03 no./ind. seasonally. When the saltwater barrage shutters were fully/partially closed during the Pre-monsoon/Northeast Monsoon, MPs in copepods were considerably larger (av. 0.11 ± 0.03 no./ind., and av. 0.075 ± 0.02 no./ind., respectively) as compared to the Southwest Monsoon (av. 0.03 ± 0.01 no./ind.), when the barrage shutters were fully open. This shows the potential of man-made flow restrictions to increase the bioconcentration of MPs in copepods and their possible transfer to higher trophic levels through the food chain, adding to the region's previous discovery that much higher trophic level resources are polluted with a high concentration of MPs.

Microplastics in zooplankton in the eastern Arabian Sea: The threats they pose to fish and corals favoured by coastal currents.

The baseline study of Microplastics (MPs) in zooplankton (copepods, chaetognaths, decapods, and fish larvae) from six different zones along India's west coast (off Kanyakumari/Cape Comorin, Kochi, Mangalore, Goa, Mumbai, and Okha) in the Eastern Arabian Sea (EAS) is presented here with their vast ecosystem impacts. This investigation revealed that zooplankton in all six zones accumulated MPs pellets (52.14%), fibres (28.40%), films (10.51%), and fragments (8.95%). The highest average retention of MPs (MPs/individual) was found in fish larvae (av. 0.57 ± 0.18) while copepods had the lowest (av. 0.03 ± 0.01). The presence of low-density polyethylene, polypropylene, polystyrene, and polyethylene terephthalate was confirmed by Raman Spectra of MPs. The MPs in zooplankton found in this study (av. 22 ± 7 pieces/m3) were nearly 2-fold greater than those found in some of the world's most densely populated areas. It is shown that the strong southerly coastal currents could advect the MPs contaminated water mass too far away, having the potential to affect the fish and corals.

Experimental approach, theoretical investigation and molecular docking of 2- chloro-5-fluoro phenol antibacterial compound.

The molecular structural dimerization of biologically potent 2-chloro-5-fluoro phenol (2C5FP) is optimized. A combined experimental and theoretical characteristics of vibrational spectral determinations (NMR, FT-IR and Raman) on 2-chloro-5-fluoro phenol (2C5FP) were used at DFT-B3LYP/6-31++G (d,p) level of computation. A close coherence is achieved when experimentally observed wave numbers are compared with calculated wave numbers by refinement of the scale factors. Calculated values of global chemical descriptors of the present molecule reveal significant molecular stability and chemical reactivity. Non-Linear optical (NLO) property of the present molecule is investigated by determining the second order non linear parameter of first hyperpolarizability ß. Moreover, hydrogen bond and thermodynamic parameters at various temperatures are determined and discussed. Investigated compound 2C5FP possesses a better antibacterial activity against Echerichia coli, Streptococcus aureus, Pseudomonas aureus,and Staphylococcus aureus, respectively. The title molecule is subjected to molecular docking studies with two different proteins, namely Staphylococcus aureus Tyrosyl-tRNA synthetase (PDB ID: 1JIL) and human dihydroorotate dehydrogenase (hDHODH) (PDB ID: 6CJF). The results of molecular docking analysis support the antibacterial activity and demonstrate a strong interaction with the DHODH inhibitor.

In silico prediction of a new lead compound targeting enolase of trypanosomatids through structure-based virtual screening and molecular dynamic studies.

Enolase is one of the key glycolytic metalloenzyme in many organisms, and it is a potential therapeutic target including trypanosomatids. Sequence and structural analysis of enolase of Trypanosoma bruzi (TbENO), Trypanosoma cruzi (TcENO) and Leishmania donovani (LdENO) revealed conserved sequence pattern and structural features. Hence identification of an inhibitor against enolase of one trypanosomatid organism may have similar effects on enolase of homologous organisms belonging to same family. In the process to identify potent inhibitor compounds against TbENO by in silico methods, compounds containing the substructures of substrate, i.e. phosphoenolpyruvate (PEP) and the well-known inhibitors, fluoro-2-phosphono-acetohydroxamate (FPAH) and phosphono-acetohydroxamate (PAH), were collected. Virtual screening and induced fit docking studies were carried out to explore compounds that have better binding affinity than PEP and FPAH. PPPi was found to be the top hit exhibiting significant binding affinity towards enolase. Glide energy values of two other compounds represented by PubChem ID: 511392 and 101803456 was in good agreement with PEP and PAH. TbENO-PPPi complex was subjected to molecular orbital analysis and molecular dynamic studies by considering its remarkable binding affinity as it could be a potent inhibitor of enolase. Despite being an endogenous compound, based on the results of this study, we highlight PPPi to be a lead compound, and its structure can be treated as a model for further chemical modifications to obtain more potent antagonists.

Quantum chemical determination of molecular geometries and spectral investigation of 4-ethoxy-2, 3-difluoro benzamide.

The present work reports the application of density functional theory (DFT) at B3LYP with various basis sets which provide the relationship between the structural and spectral properties of 4-ethoxy-2, 3-difluoro benzamide (4EDFB). A Complete vibrational analysis has been performed at the density functional theory (DFT) method with various basis sets in the ground state. The results of vibrational wave numbers are in good agreement with the experimental spectra (Infrared and Raman). Energy gap of the molecule is evaluated using frontier molecular orbital energies (HOMO-LUMO). The frontier energy gap value reveals the chemical reactivity and intermolecular charge transfer occur within the molecule. Global chemical descriptors provide the local and global softness and local reactivity parameters used to identify the nucleophilic and electrophilic behavior of a specific site within the compound. The dimer structure is performed to evaluate the intermolecular hydrogen bond (O-H-O). The title molecule is capable of receiving second harmonic generation (SHG) is due to high value of hyperpolarizability indicates the NLO activity of the molecule. Apart from NLO entities, aromaticity and the molecular electrostatic potential surface (MEP) explain the hydrogen bonding and provide the reactive behavior of the molecule. The Mulliken population analysis leads to redistribution of electron density in the ring.

Isochamanetin is a Selective Inhibitor for CyclinD1 in SKOV3 Cell Lines.

The cyclinD1 is an emerging potent therapeutic drug target in the treatment of ovarian cancer. CyclinD1, Cdks phosphorylation regulates cell cycle and controls transcription. For this reason, CyclinD1 have been subject to extensive cell cycle- related research, and consequently various therapeutic inhibitor drugs have been developed to these protein targets. In the present study we identified that the expression levels of Bcl-2, Bax, caspase 8, 9 and cyclinD1 using Q-PCR method in SKOV3 cell lines treated with Isochamanetin. The viability and migratory inhibition ability also studied to know the mode of cell death. Further the expression levels of Bcl-2, caspase8,9, Cytochrome C and CyclinD1 were significantly down regulated in SKOV3 cancer cells treated with isochamanetin, a specific binding molecule to CyclinD1. The therapeutic molecules found by a high through put insilicoscreen of this pocket exhibit cytostatic nature and reduce protein levels of cell cycle. The novel structural site on CyclinD1, which is well conserved and inhibits the SKOV3 cells from G0-G1 to S phase cell cycle progression. The current result suggests that isochamanetin serves as potent binding agent to the cyclinD1.

Effects of increased accumulation of doxorubicin due to emodin on efflux transporter and LRP1 expression in lung adenocarcinoma and colorectal carcinoma cells.

Treatment with doxorubicin (dox) and emodin, separately and together, under normoxic and hypoxia-like conditions induced by CoCl2, led to greater intracellular compound accumulation over 10 h post-addition in the presence of CoCl2 in lung adenocarcinoma (A549) and colorectal carcinoma (HCT-15) cell lines. Confocal microscopy revealed that emodin, by itself, showed high cytosolic distribution in both cell lines, at 40 min post-addition but had entered the nuclei by 2 h, while dox entered the nuclei by 40 min. Both compounds modulated the expression of the efflux transporters (PgP, ABCG2, or MRP1-4) and the endocytic receptor, low-density lipoprotein receptor-related protein 1 (LRP1), to different extents under the study conditions. Efflux transporter upregulation was linked to lower intracellular compound levels due to greater efflux. Increased dox accumulation was accompanied by unaltered expression or upregulation of LRP1 in A549 cells. In both cell lines, increased accumulation of dox and emodin was observed whenever LRP1 and the efflux transporters known to transport dox and emodin were all up- or downregulated concomitantly. Increased growth inhibition was linked to co-treatment with dox and emodin and with increased ligand accumulation. The results presented in this study raise the hypothesis that higher production of LRP1 protein may be associated with higher endocytosis of upregulated transporter proteins at the cell surface, and hence, increased dox and emodin accumulation and growth inhibition. If so, elevation of LRP1 expression may be a useful target for interventions to promote the efficacy of these and other anticancer drugs.

A Review of Stapled Peptides and Small Molecules to Inhibit Protein-Protein Interactions in Cancer.

Disruption of binding of two or more molecules to a protein surface is a common basis of inhibition of many biological activities. Smallmolecule inhibitors, antibodies, proteins, and peptidomimetics have been examined as ways to antagonize receptor activity. The peptide α-helix plays a crucial role in the function of many proteins. Hence, much effort has been invested in mimicking α-helices at the binding interface of two proteins to competitively inhibit their interactions. Peptide stapling involves choosing two amino acids on the same face of a native peptide sequence for substitution with non-native amino acids whose side chains can be "stapled" together. The focus of this review is to survey the prevalence in literature of stapled peptides and small-molecule antagonists of interactions of selected mammalian cancer targets, such as ß-catenin, BH3-only members of the Bcl-2 family of proteins, eIF4E/G, estrogen receptor complexes, EZH2, Mdm2, Notch, p110α, and survivin. The increasing interest in protein targets currently considered to be "undruggable" with greater selectivity for existing targets, with the goal of overcoming the omnipresent problem of resistance, could be served well by utilizing information about protein-protein interactions to develop both small-molecule and stapled peptide inhibitors.

Small molecules for immunomodulation in cancer: a review.

Small-molecule cytotoxic agents are already in use for cancer immunotherapy in the form of antibody conjugates containing these molecules linked covalently to antibodies or their fragments with the goal of targeting specific surface components of tumor cells. However, there are also reports of small molecules that act as antagonists to surface enzyme-linked receptors and receptors that interact with the tumor microenvironment, or that even inhibit metabolic enzymes. Such molecules have been shown to directly inhibit the signaling initiated by the respective ligands binding to their receptors, to recruit antibodies and other immunomodulatory molecules, or to promote or inhibit the proliferation of different immune cells to target specific types of cancer cells. This review will discuss immune response modifiers such as imiquimod, antibody-recruiting molecules that target prostate cancer, integrin receptor antagonists, indoleamine-2,3-dioxygenase inhibitors, emodin, RORÉ£t antagonists, ephrin receptor antagonists, membrane-bound carbonic anhydrase IX (CAIX) inhibitors, and selected protein kinase inhibitors. These small molecules can open up new ways to treat many types of cancers and possibly even other diseases that arise from immune dysregulation. Finally, the review will briefly discuss some additional targets that are being pursued to modify immune system responses in the tumor microenvironment.

Exploration of effects of emodin in selected cancer cell lines: enhanced growth inhibition by ascorbic acid and regulation of LRP1 and AR under hypoxia-like conditions.

This study explores the link between the antiproliferative activity of emodin through the generation of reactive oxygen species (ROS) in various cancer cell lines and the expression of the androgen receptor (AR) in the prostate cancer cell lines LNCaP (androgen-sensitive) and PC-3 (androgen-refractory), as well as the pro-metastatic low-density lipoprotein receptor-related protein 1 (LRP1) in the above prostate cancer cells and the nonprostate cell lines A549 (lung), HCT-15 (colon) and MG-63 (bone) under normoxic and hypoxia-like conditions. Among all cell lines, emodin showed most growth inhibition in LNCaP, followed by A549. The mechanism of cytotoxicity of emodin was postulated to be the widely reported ROS generation, based on the observations of poor in vitro radical-scavenging activity and increased growth inhibition of emodin by ascorbic acid (AA) pre-treatment owing to the additive effects of ROS generation by emodin and pro-oxidant effects of AA. Emodin downregulated AR in LNCaP under normoxic and hypoxia-like conditions (simulated by CoCl(2)) and LRP1 under normoxia. Emodin upregulated LRP1 in other cell lines, except HCT-15, under normoxic, and even more markedly under hypoxia-like conditions. The downregulation of AR in LNCaP and upregulation of LRP1 in all cell lines, except HCT-15, under hypoxia-like conditions along with growth inhibition by emodin, suggests that emodin may be a useful therapeutic option against androgen-sensitive prostate cancer and other such LRP1-expressing cancers to attempt the targeting of the elevated LRP1 levels to allow the uptake of emodin and/or any other accompanying therapeutic agents by LRP1.

Antioxidant Activity and Gas Chromatographic-Mass Spectrometric Analysis of Extracts of the Marine Algae, Caulerpa peltata and Padina Gymnospora.

The results of our previous investigations on extracts of selected marine algae showed that Caulerpa peltata and Padina gymnospora had more promising antiproliferative and antioxidant activities than Gelidiella acerosa and Sargassum wightii. Based on these results, the more active chloroform extract of C. peltata and ethyl acetate extract of P. gymnospora were further analyzed for their constituents by using gas chromatography in tandem with mass spectrometry. The GC-MS analysis (GC % peak area given in parentheses) showed that fucosterol (12.45%) and L-(+)-ascorbic acid 2, 6-dihexadecanoate (8.13%) were the major compounds present in P. gymnospora ethyl acetate extract. On the other hand, C. peltata chloroform extract had 1-heptacosanol (10.52%), hexacosanol acetate (9.28%), tetradecyl ester of chloroacetic acid (7.22%), Z,Z-6, 28-heptatriactontadien-2-one (6.77%) and 10, 13-dimethyl-methyl ester of tetradecanoic acid (5.34%) as major compounds. Also described in the report are the beta-carotene bleaching inhibitory and total reducing activities of the chloroform and ethyl acetate extracts of C. peltata and P. gymnospora, respectively, relative to the other three extracts (aqueous, methanol, chloroform or ethyl acetate) of the two algae.

Differential growth inhibition of cancer cell lines and antioxidant activity of extracts of red, brown, and green marine algae.

As the use of various anticancer drugs is associated with many undesirable side effects, there is an urgent need for the discovery of new, better, and specific anticancer compounds. Antioxidant and antiproliferative activities as well as effects on cell morphology were investigated for methanol (M), chloroform (C), ethyl acetate (E), and aqueous (A) extracts of Caulerpa peltata, Gelidiella acerosa, Padina gymnospora, and Sargassum wightii using 2,2-diphenyl-1-picrylhydrazyl radical-scavenging, ferrous ion chelation, and resazurin-based growth inhibition (in A549, HCT-15, MG-63, and PC-3 cell lines) assays. A general trend was the greater extraction of phenols and flavonoids by chloroform and ethyl acetate, which showed higher activity in many assays. These non-polar C and E extracts showed higher DPPH radical-scavenging and growth inhibitory activities in A549, HCT-15, and PC-3 cells. However, higher ferrous ion chelation (A extracts) and growth inhibition in MG-63 cells (M and A extracts) were seen for the polar extracts. Furthermore, P. gymnospora and C. peltata emerged as promising sources for antiproliferative agents that could be explored for their own activity and as leads for the development of other compounds.

Hypoglycemic effect of Mucuna pruriens seed extract on normal and streptozotocin-diabetic rats.

The hypoglycemic effect of the aqueous extract of the seeds of Mucuna pruriens was investigated in normal, glucose load conditions and streptozotocin (STZ)-induced diabetic rats. In normal rats, the aqueous extract of the seeds of Mucuna pririens (100 and 200 mg/kg body weight) significantly (P<0.001) reduced the blood glucose levels after an oral glucose load from 127.5+/-3.2 to 75.6+/-4.8 mg% 2 h after oral administration of seed extract. It also significantly lowered the blood glucose in STZ diabetic rats from 240.5+/-7.2 to 90.6+/-5.6 mg% after 21 days of daily oral administration of the extract (P<0.001). Thus, this study shows that M. pruriens has an anti-hyperglycemic action and it could be a source of hypoglycemic compounds.

Measurement of protein tyrosine phosphorylation in cell adhesion.

This chapter describes biochemical, immunochemical, and microscopic approaches to measure protein tyrosine phosphorylation after cell adhesion. We have outlined detailed procedures to biochemically examine the phosphotyrosine content of cellular proteins by Western blotting, which in some cases can be performed using phospho-specific antibodies. Furthermore, we have described in detail the examination of subcellular localization of phosphotyrosine-containing proteins in focal adhesions using immunofluorescence. Finally, a quantitative fluorescence microscopic technique using an SH2-containing phosphotyrosine reporter to monitor tyrosine phosphorylation in focal adhesions in live cells is described.

The focal adhesion targeting domain of focal adhesion kinase contains a hinge region that modulates tyrosine 926 phosphorylation.

The focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK) is critical for recruitment of FAK to focal adhesions and contains tyrosine 926, which, when phosphorylated, binds the SH2 domain of Grb2. Structural studies have shown that the FAT domain is a four-helix bundle that exists as a monomer and a dimer due to domain swapping of helix 1. Here, we report the NMR solution structure of the avian FAT domain, which is similar in overall structure to the X-ray crystal structures of monomeric forms of the FAT domain, except that loop 1 is longer and less structured in solution. Residues in this region undergo temperature-dependent exchange broadening and sample aberrant phi and psi angles, which suggests that this region samples multiple conformations. We have also identified a mutant that dimerizes approximately 8 fold more than WT FAT domain and exhibits increased phosphorylation of tyrosine 926 both in vitro and in vivo.

CCAAT/enhancer-binding protein-beta has a role in osteoblast proliferation and differentiation.

CCAAT/enhancer binding protein beta (C/EBPbeta) is known to play an important role in the expression of several genes necessary for bone development and homeostasis including osteocalcin, IGF-1, and IL-6. In this study, we show that C/EBPbeta protein levels and, consequently, DNA-binding activity are temporally regulated, dramatically decreasing upon differentiation of MC3T3-E1 mouse osteoblasts. Corresponding with these results, the constitutive expression of C/EBPbeta LAP in MC3T3-E1 osteoblasts increased proliferation and suppressed osteogenic differentiation. Thus, C/EBPbeta LAP not only appears to participate in the regulation of genes associated with mature bone physiology, but is also a critical regulator of osteoblast growth and differentiation.

Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate kinase by Src regulates an integrin-talin switch.

Engagement of integrin receptors with the extracellular matrix induces the formation of focal adhesions (FAs). Dynamic regulation of FAs is necessary for cells to polarize and migrate. Key interactions between FA scaffolding and signaling proteins are dependent on tyrosine phosphorylation. However, the precise role of tyrosine phosphorylation in FA development and maturation is poorly defined. Here, we show that phosphorylation of type Igamma phosphatidylinositol phosphate kinase (PIPKIgamma661) on tyrosine 644 (Y644) is critical for its interaction with talin, and consequently, localization to FAs. PIPKIgamma661 is specifically phosphorylated on Y644 by Src. Phosphorylation is regulated by focal adhesion kinase, which enhances the association between PIPKIgamma661 and Src. The phosphorylation of Y644 results in an approximately 15-fold increase in binding affinity to the talin head domain and blocks beta-integrin binding to talin. This defines a novel phosphotyrosine-binding site on the talin F3 domain and a "molecular switch" for talin binding between PIPKIgamma661 and beta-integrin that may regulate dynamic FA turnover.